ARTICLE | doi:10.20944/preprints202307.1305.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Hypercholesterolemia; Atherosclerosis; vegetable oils
Online: 20 July 2023 (03:20:38 CEST)
Dyslipidemia presents high levels of serum cholesterol, being characterized as a risk factor for cardiovascular diseases, especially for the development of atherosclerosis. E. oleracea (OFEO), A. esculentus (OFAE), B. orellana (OFBO) and granulated (CHR) oils are rich in bioactive compounds with potential to treat changes in lipid metabolism. This study investigated the effects of treatments with oils from A. esculentus, E. oleracea, B. orellana and granules (Chronic SM®) on saturated fat-induced dyslipidemia Cocos nucifera L. The chromatographic profile showed the majority of unsaturated fatty acids in the tested oils. The quantification of tocotrienols and geranylgeraniol was obtained in OFBO and CHR. Treatments with OFEO, OFAE, OFBO and CHR were able to significantly reduce glycemia with p>0.001, as well as hypertriglyceridemia, total cholesterol and LDL-cholesterol, in addition to increasing HDL-cholesterol. The treatments inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats. The obtained results suggest that the OFEO, OFAE, OFBO and CHR groups have antidyslipidemic effects and antiatherogenic activity.
REVIEW | doi:10.20944/preprints202105.0735.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Curcumin; atherosclerosis; pharmacology; therapeutics
Online: 31 May 2021 (10:40:39 CEST)
Curcumin, a hydrophobic bioactive constituent from Curcuma longa, has several health promoting properties including anti-atherosclerotic properties. Further, curcumin has blood glucose- and lipid-lowering properties, prophylactic, and therapeutic effects in other cardiometabolic diseases. Atherosclerosis is an umbrella term for a series of degenerative and hyperplasic lesions such as thickening or sclerosis in large and medium -sized artery walls that decrease vascular-wall elasticity and lumen diameter. The atherosclerotic cerebro-cardiovascular disease has become a major concern to human health in recent years. Considering the notable cardiovascular actions of curcumin, the present review summarizes the current status and future perspective of research on curcumin and its ability to prevent or treat atherosclerosis
REVIEW | doi:10.20944/preprints202012.0136.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Platelet; microbiota; TMA; Atherosclerosis
Online: 7 December 2020 (10:34:31 CET)
Emerging data have demonstrated a strong association between the gut microbiota and the development of cardiovascular disease (CVD) risk factors such as atherosclerosis, inflammation, obesity, insulin resistance, platelet hyperactivity, and plasma lipid abnormalities. Several studies in humans and animal models have demonstrated an association between gut microbial metabolites, such as trimethylamine-N-oxide (TMAO), short-chain fatty acids, and bile acid metabolites, amino acid breakdown products, with CVD. Human blood platelets are a critical contributor to the hemostatic process. Besides, these blood cells play a crucial role in developing atherosclerosis and, finally, contribute to cardiac events. Since the TMAO, and other metabolites of the gut microbiota, are associated with platelet hyperactivity, lipid disorders, and oxidative stress, the diet-gut microbiota interactions have become an important research area in the cardiovascular field. Platelets became hyperactive in people with diabetes mellitus, sedentary lifestyle, obesity, and insulin resistance and exhibited increased sensitivity at a baseline level and in response to agonists, ultimately contributing to increased aggregation plaque development. In addition to these factors, TMAO also contributes to platelet hyperactivity. Several approaches are now suggested to reduce plasma TMAO levels, such as microbiota modulation using probiotics, prebiotics, and oral broad-spectrum antibiotics. This review describes the association between microbiota-derived metabolites and CVD development.
REVIEW | doi:10.20944/preprints202208.0295.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: coronary; atherosclerosis; cardiac CT; geometry
Online: 17 August 2022 (03:24:46 CEST)
Coronary artery disease (CAD) represents a modern pandemic associated with significant morbidity and mortality. The multi-faceted pathogenesis of this entity has long been investigated, highlighting the contribution of systemic factors such as hyperlipidemia and hypertension. Nevertheless, recent research has drawn light to the importance of geometrical features of coronary vasculature on the complexity and vulnerability of coronary atherosclerosis. Various parameters have been investigated so far, including vessel-length, cross-sectional area, curvature, and tortuosity, using primarily invasive angiography and recently non-invasive cardiac computed tomography angiography (CCTA). It is clear that there is correlation between geometrical parameters and both the haemodynamic alterations augmenting the atherosclerosis-prone environment and the extent of plaque burden. The purpose of this review is to discuss the currently available literature regarding this issue and propose a potential non-invasive imaging biomarker, the geometric risk score, which could be of importance to allow early detection of individuals at increased risk of developing CAD.
REVIEW | doi:10.20944/preprints201808.0149.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: atherosclerosis, mesenchymal stem cells, inflammation
Online: 7 August 2018 (23:22:20 CEST)
Atherosclerosis is a chronic inflammatory disease which results in thickening of the vessel wall and narrowing of the lumen. It is a leading cause of death worldwide. Preventive treatment is taken into prioritized consideration since currently no effective approaches to cure atherosclerosis are available. These treatments mainly focus on lowering blood cholesterol levels, especially LDL-C, by statins. Even so, lowering lipid levels is not sufficient to reduce the risk of cardiovascular events in all patients. Recently, atherosclerosis has increasingly been recognized as a chronic inflammatory disease involving the immune system, initiating new therapeutic approaches which could alleviate or prevent atherosclerosis by modulating inflammation. Mesenchymal stem cells (MSCs) have emerged as a promising option to relieve inflammation and balance immune responses in inflammatory diseases. Several studies including our group also reported that MSCs may be a new therapeutic option for atherosclerosis. This review summarizes the updated state of our knowledge in the administration of MSCs to alleviate atherosclerosis and discusses some of the key unresolved challenges that need to be solved in future studies.
ARTICLE | doi:10.20944/preprints202308.1544.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: atherosclerosis; Tibetan minipig; Untargeted metabolomics,; Biomarkers
Online: 22 August 2023 (10:46:40 CEST)
Background: Atherosclerosis (AS) is a chronic progressive disease caused by lipometabolic disorder. However, the pathological characteristics and mechanism of AS have not been fully clarified. By high fat and cholesterol diet induction, Tibetan minipig could be developed to the AS model animal which had a very similar pathogenesis to human AS. Methods: Here, we built the AS model of Tibetan minipigs and identified the differential abundance metabolites in the development of AS based on untargeted metabolomics. Results: We found that the sphingolipid metabolism and glucose oxidation were enriched in the AS group and the phenylalanine metabolism was reduced in the AS group. Moreover, in the development of AS, gluconolactone was enriched in the late stage of AS whereas biopterin was enriched in the early stage of AS. Conclusion: Gluconolactone and biopterin could be potential biomarkers for indicating the development of AS. Our research provides novel clues for the metabolic mechanism of AS from the perspective of metabolomics.
CASE REPORT | doi:10.20944/preprints202302.0260.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-CoV-2; atherosclerosis
Online: 16 February 2023 (02:18:09 CET)
Patients with COVID-19 demonstrate higher rates of cardiovascular complications, including thromboses and thromboembolism. One may suppose that the action of SARS-CoV-2 transforms stable atherosclerotic plaques into unstable status. Cardiovascular complications in COVID-19 may be caused by progressive viral alteration the blood vessels, including vasa vasorum. A lethal case of ischemic brain disease caused by cerebral atherosclerosis and exacerbated with a stroke during COVID-19 infection is briefly described. The results of autopsy showed perivascular lymphocytic infiltration and signs of vasa vasorum vasculitis with thrombi of adventitial microvasculature. The data discussed in the article are interpreted in context of the concept giving the important role in atherogenesis to vasa vasorum.
REVIEW | doi:10.20944/preprints202009.0301.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Atherosclerosis; Phospholipases; Macrophages; T cells; Lipins
Online: 13 September 2020 (23:45:55 CEST)
Phospholipases are a family of lipid altering enzymes that can either reduce or increase bioactive lipid levels. Bioactive lipids elicit signaling responses, activate transcription factors, promote g-coupled protein activity, and modulate membrane fluidity that mediate cellular function. Phospholipases and the bioactive lipids they produce are important regulators on immune cell activity, dictating both pro-inflammatory and pro-resolving activity. During atherosclerosis, pro-inflammatory and pro-resolving activities govern atherosclerosis progression and regression respectively. This review will look at the interface of phospholipase activity, immune cell function, and atherosclerosis.
BRIEF REPORT | doi:10.20944/preprints202001.0280.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: atherosclerosis; vascular biology; calcification; genetics; 9p21
Online: 24 January 2020 (11:17:21 CET)
Background: Genome-wide association studies have identified the chromosome 9p21 locus as one of the most important genetic risk factors for cardiovascular disease. However, the mechanism by which this locus promotes disease remains unclear due to difficulty identifying the causal genes and lack of a suitable animal model. Methods and Results: A total of 180 coronary artery autopsy specimens were analyzed histopathologically. The genotype of 9p21 (rs1333049) was not associated with any coronary risk factors nor the vulnerable plaque phenotype, but carriers of 9p21 risk allele did demonstrate more lesional calcification. To extend these studies into an animal model, mice with a targeted deletion of the orthologous 70-kb non-coding interval on chromosome 4 (chr4D70kb/D70kb) were bred onto ApoE-/- and fed with high fat diet. Targeted deletion of the 9p21 risk interval increased susceptibility to atherosclerotic plaque progression, but did not affect plaque rupture in the tandem stenosis model. Coronary risk factors such as body weight, blood pressure, lipid, and glucose levels did not differ between genotypes. Von Kossa staining revealed that chr4D70kb/D70kb, ApoE-/- developed more calcification in the plaque compared with chr4+/+, ApoE-/- mice, and that this this change was accompanied by increased aortic mRNA expression of Runx2, a key osteogenic transcription factor. Primarily cultured smooth muscle cells from chr4D70kb/D70kb were hyperproliferative, and showed a calcification-prone phenotype after exposure to high-phosphate medium. Treatment with Palbociclib, a selective inhibitor of cyclin-dependent kinase 4/6, reduced mRNA expression of osteogenic genes in smooth muscle cells. Conclusion: Results from human and mouse studies indicate that the 9p21 non coding risk interval is associated with larger atherosclerotic plaque burden, but not with plaque rupture. 9p21 may promote lesion expansion by inducing the proliferation of de-differentiated and osteogenic smooth muscle cells.
CASE REPORT | doi:10.20944/preprints202311.1336.v1
Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: Pneumatosis intestinalis; Thrombosis; CT Scan; Atherosclerosis; Ischemia
Online: 21 November 2023 (13:43:57 CET)
Pneumatosis intestinalis is the presence of air within the two layers of the wall of the gastrointestinal tract, specifically in the small and large intestines. This accumulation of gas can cause thicker walls of the intestines in X-ray or CT scans. Superior Mesenteric Artery (SMA) Thrombosis occurs due to the formation of blood clots within the SMA. As it supplies from the ampulla in the second part of the duodenum to the splenic flexure of the large intestine its thrombosis can cause ischemia in any part depending upon its branch. A 67-year-old male patient presented to the hospital with the complaint of generalized abdominal pain for 5 days along with fever, nausea, vomiting, obstipation, and postprandial fullness. On further investigation with the help of an MDCT scan and X-ray, proximal jejunal loops showed circumferential air within the walls giving the diagnosis of Pneumatosis Intestinalis along with Superior Mesenteric Artery Thrombosis causing jejunal infarct.
ARTICLE | doi:10.20944/preprints202309.1343.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: cIMT; weight change; prospective cohort; atherosclerosis; CLSA
Online: 20 September 2023 (10:22:15 CEST)
To explore impact of weight change (WC) on risk of atherosclerosis measured by cIMT, 20,700 participants from the CLSA follow-up were included in analysis. WC was defined as the difference of weight measured at follow-up and baseline, then quartered into four groups (Q1–Q4). cIMT>1.0 mm was defined as high-risk for atherosclerosis. Adjusted odds ratio (OR, [95% CI]) from logistic regression models were used to evaluate the association between WC and risk of atherosclerosis. At follow-up, participants have gained 0.118 kg weight, on average, and 16.4% of them were at high-risk for atherosclerosis. The mean levels of cIMT were comparable between participants from Q1 to Q4. Compared to Q2 (reference), the ORs (95% CI) were 1.00 (0.86, 1.15), 1.19 (1.03,1.38), and 1.25 (1.08,1.45) for Q1, Q3, and Q4, respectively. A similar pattern was observed when analyses conducted by <65 vs. 65+ years separately, but it was weaker for those aged 65+ years. Results from the jointed distribution analyses indicated that weight loss might increase risk for atherosclerosis among participants with obese at baseline, but not for those with cardiovascular events status at baseline. Weight gain, however, would increase risk for atherosclerosis regardless of cardiovascular events status, or overweight/obese at baseline.
REVIEW | doi:10.20944/preprints202309.0797.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: atherosclerosis; innate immunity; signaling pathways; trained immunity
Online: 13 September 2023 (07:54:33 CEST)
Innate immune pathways play a crucial role in the development of atherosclerosis, from sensing initial danger signals to the long-term reprogramming of immune cells. Despite the success of lipid-lowering therapy, anti-hypertensive medications, and other measures in reducing complications associated with atherosclerosis, cardiovascular disease (CVD) remains the leading cause of death worldwide. Consequently, there is an urgent need to devise innovative preventive and therapeutic strategies to alleviate the global burden of CVD. Extensive experimental research and epidemiological studies have demonstrated the dominant role of innate immune mechanisms in the progression of atherosclerosis. Recently, landmark trials including CANTOS, COLCOT, and LoDoCo2 have provided solid evidence, demonstrating that targeting innate immune pathways can effectively reduce the risk of CVD. These groundbreaking trials mark a significant paradigm shift in the field and open new avenues for atheroprotective treatments. It is therefore crucial to comprehend the intricate interplay between innate immune pathways and atherosclerosis for the development of targeted therapeutic interventions. Additionally, unraveling the mechanisms underlying the long-term reprogramming may offer novel strategies to reverse the pro-inflammatory phenotype of immune cells and restore immune homeostasis in atherosclerosis. In this Review, we present an overview of the innate immune pathways implicated in atherosclerosis, with a specific focus on the signaling pathways driving chronic inflammation in atherosclerosis and the long-term reprogramming of immune cells within the atherosclerotic plaque. Elucidating the molecular mechanisms governing these processes presents exciting opportunities for the development of a new class of immunotherapeutic approaches aimed at reducing inflammation and promoting plaque stability. By addressing these aspects, we can potentially revolutionize the management of atherosclerosis and its associated cardiovascular complications.
REVIEW | doi:10.20944/preprints202308.1970.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: cardiovascular health; gut microbiota; microbiome; dysbiosis; atherosclerosis
Online: 30 August 2023 (03:54:51 CEST)
Cardiovascular disease (CVD), comprising heart and blood vessel disorders, persists as the foremost contributor to global morbidity and mortality. In modern times, the intricate composition of gut microbiota has garnered significant focus, particularly for its varying impact on diverse ailments. Perturbations in gut microbiota and consequent dysbiosis have demonstrated connections with the advancement and origin of CVD, including conditions like atherosclerosis, hypertension, and heart failure. This comprehensive review delves into the pivotal role of gut microbiota in maintaining cardiovascular well-being.
ARTICLE | doi:10.20944/preprints202307.1819.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Atherosclerosis; pinX1; MMP-9; p66shc; oxidative stress
Online: 27 July 2023 (09:34:39 CEST)
Atherosclerosis (AS) is an age-related disease. Mitochondria and telomere links have been considered to play important roles in AS. PinX1 is a potent and highly conserved endogenous telomerase inhibitor. However, the role of pinX1 in AS and its role in oxidative stress have not been reported. In order to investigate the role of pinX1 in AS, we established a classical AS mice model in the present work and increased pinX1 protein expression using pinX1 overexpression adeno-virus by tail vein injection. Then, red-oil O and HE staining were employed to evaluate the severity of AS. Serum lipid profile and oxidative stress were also detected by using its specific chemical testing kit. The results indicated that high-fat diet (HFD) markedly decreased pinX1 and increased p66shc protein expression, whereas overexpression of pinX1 protein expression in mice produced the opposite results. In addition, pinX1 significantly minimized plaque area and alleviated the abnormal serum lipid profile. By using Western blot and Biochemical assay kits, overexpression of pinX1 decreased p66shc and MMP-9 protein expression and reduced oxidative stress. This study showed pinX1 can inhibit p66shc, MMP-9, and related oxidative stress, pinX1 may be considered as a new candidate target for the treatment of AS.
ARTICLE | doi:10.20944/preprints202104.0154.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Atherosclerosis; Gallic acid; Chlorogenic acid,; Microbiota; Trimethylamine
Online: 5 April 2021 (16:28:50 CEST)
Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). Reduction of TMA formation has been shown to provide to cardioprotective effects, and some phytochemicals may produce such reduction. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20 % fecal slurry (1:10 in PBS), 100 M choline, and 12 h fermentation. Also, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50 % reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80 -90 % in. TMA production inhibition), with IC50 around 5 mM. Nor DMB neither gallic acid and chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA lyase activity or expression.
ARTICLE | doi:10.20944/preprints202103.0733.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: thoracic aorta; atherosclerosis; vascular calcification; risk factors
Online: 30 March 2021 (11:42:32 CEST)
Thoracic aortic calcium (TAC) appears to be a subclinical marker of cardiovascular disease (CVD) and to predict CV mortality. However, studies on TAC use tomographic scans obtained for coronary artery calcium (CAC) score, which does not include the aortic arch. This study evaluates TAC prevalence in aortic arch (AAC), ascending (ATAC) and descending thoracic aorta (DTAC) and verify whether they are associated with the same CV risk factors. Cross-sectional analysis, including 2,427 participants (mean age 55.6 ± 8.7; 54,1% women) of the ELSA-Brasil cohort. Nonenhanced ECG-gated tomographies were performed in 2015-2016. Multivariable logistic regression estimated the CV risk factors associated with calcium in each segment. Overall prevalence of ATAC, AAC and DTAC was, 23,1%, 62.1%, and 31.2%, respectively. About 90.4% of the individuals with TAC had AAC and only 19.5% had calcium in all segments. In the multivariable analysis, increasing age, lower levels of schooling, current smoking, higher body mass index, and hypertension remained associated with calcium in all segments. No sex or race/ethnicity differences were found in any aortic segment. Diabetes and Dyslipidemia were associated with ATAC and DTAC, but not with AAC, suggesting that AAC may reflect an overlap of mechanisms that impact vascular health, including atherosclerosis.
ARTICLE | doi:10.20944/preprints202309.0464.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: carotid atherosclerosis; macrophage; intraplaque neovascularization; atherothrombosis; intraplaque hemorrhage
Online: 7 September 2023 (10:47:14 CEST)
Background: Atherosclerosis is a progressive disease that results from a combination of endothelial dysfunction and inflammatory arterial wall disorder. Stenosis of the carotid artery caused by atherosclerotic plaques is responsible for approximately 10-20% of strokes and transient ischemic attacks, and the low-grade intraplaque inflammation interferes with lesion stability and progression. Methods: In this cohort study, initially, 119 patients were enrolled who underwent carotid endarterectomy. Of these, 67 cases with active perilesional inflammatory infiltrate were chosen for further immunohistochemical examination. The CD68+ infiltrate, iNOS2+, Arg1, and CD31 expressions were quantified around the lipid core by digital morphometry. These results were correlated with the presence of morphological changes leading to plaque instability: ulceration, thrombosis, intraplaque hemorrhage, the presence of the lipid core, calcification, and neovascularization. Results: Patients with a stronger macrophage CD68+ infiltrate were associated with intraplaque hemorrhage (p=0.003). In 12 cases with dominant iNOS2 positivity, the occurrence of atherothrombosis was significantly more frequent (p=0.046). Plaque neovascularization, characterized by CD31+, was correlated with atherothrombosis (p=0.02). Conclusion: The intensity of macrophage infiltration correlates with intraplaque hemorrhage, and the presence of pro-inflammatory iNOS2+ macrophages is associated with atherothrombosis in endarterectomized carotid plaques. Neovascularization also has potential thrombotic capacity.
REVIEW | doi:10.20944/preprints202307.1056.v1
Subject: Medicine And Pharmacology, Internal Medicine Keywords: atherosclerosis; inflammation; peripheral artery disease; glycocalyx; endothelial dysfunction
Online: 17 July 2023 (05:31:19 CEST)
Inflammation has a critical role in the development and progression of atherosclerosis. On the molecular level, inflammatory pathways negatively impact endothelial barrier properties and thus tissue homeostasis. Conformational changes and destruction of the glycocalyx further promote proinflammatory pathways also contributing to procoagulability and a prothrombotic state. In addition, changes in the extracellular matrix composition lead to (peri-)vascular remodelling and alterations of the vessel wall, e.g., aneurysm formation. Moreover, progressive fibrosis leads to reduced tissue perfusion due to loss of functional capillaries. The present review aims at discussing molecular and clinical effects of inflammatory processes on the micro- and microvas-culature with a focus on peripheral artery disease.
ARTICLE | doi:10.20944/preprints202306.0111.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: lipoprotein(a); PCSK9; PCSK9-Lp(a); monocytes; atherosclerosis
Online: 2 June 2023 (01:56:57 CEST)
In this study we analyzed the concentration of lipoprotein(a) [Lp(a)], PCSK9-Lp(a) complexes and the circulating monocyte subsets in coronary atherosclerosis. 257 patients with coronary atherosclerosis (CA) and 68 patients without stenotic atherosclerosis in the coronary, carotid and lower extremity arteries (control group) were enrolled. Monocyte subpopulations (classical CD14++CD16-, intermediate CD14++CD16+, non-classical CD14+CD16+) were analyzed by direct immunofluorescence and flow cytometry. Lp(a) and PCSK9-Lp(a) complexes in serum were detected by ELISA. The concentration of Lp(a) was higher in CA group compared to controls (23.0 (9.1;73.3) mg/dL versus 10.7 (4.7;25.0) mg/dL, p<0.05). No correlations between the level of Lp(a) and the concentration of PCSK9-Lp(a) complexes, nor between the level of Lp(a) or PCSK9 and the total number of monocytes were observed in both groups. A slight positive correlation between the concentration of PCSK9-Lp(a) complexes and the absolute level of monocytes was obtained (r=0.20, p=0.002) in patients with atherosclerosis predominantly due to intermediate monocyte subsets (r=0.33, p=0.04). According to regression analysis both PCSK9-Lp(a) complex concentration and BMI were related to the absolute number of blood monocytes in patients with atherosclerosis. Further studies are required to determine the pathogenetic contribution of PCSK9-Lp(a) complexes to the development of atherosclerosis.
ARTICLE | doi:10.20944/preprints202305.1481.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: atherosclerosis; 20(S)-PPT; PCSK9; LDLR; Panax notoginseng
Online: 22 May 2023 (09:02:18 CEST)
Atherosclerosis (AS) is a chronic progressive disease caused by various factors, and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is the primary goal in preventing and treating AS. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a crucial role in regulating LDL-C metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S) -protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by western blotting, real time-polymerase chain reaction (RT-PCR), Enzyme-linked Immunosorbent Assay (ELISA), immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low density lipoprotein receptor (LDLR) protein levels, promoted LDL uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of FoxO3 protein and mRNA and decreasing the levels of HNF1α protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic αSMA expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol fed in ApoE-/- mice (HCF group). Additionally, 20(S)-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the HCF group. The study revealed that 20(S)-PPT inhibited LDLR degradation via PCSK9 to alleviate AS.
ARTICLE | doi:10.20944/preprints202008.0083.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: scavenger receptor CD36; inflammation; vascular calcification; diabetes; atherosclerosis
Online: 4 August 2020 (10:37:01 CEST)
Diabetes mellitus entails increased atherosclerotic burden and medial arterial calcification but the precise mechanisms are not fully elucidated. Our aim was to investigate the implication of CD36 in inflammation and calcification processes orchestrated by vascular smooth muscle cells (VSMCs) under hyperglycemic and atherogenic conditions. We examined the expression of CD36, pro-inflammatory cytokines, endoplasmic reticulum (ER) stress markers and mineralization-regulating enzymes by RT-PCR in human VSMCs, cultured in medium containing normal (5 mM) or high glucose (22 mM) for 72 h with or without oxLDL (24 h). The uptake of DiI-labelled oxLDL was quantified by flow citometry and fluorimetry and calcification assays were performed in VSMC cultured in osteogenic medium and stained by alizarin red. We observed an induction in the expression of CD36, cytokines, calcification markers and ER stress markers under high glucose that was exacerbated by oxLDL. These results were confirmed in carotid plaques from subjects with diabetes versus non-diabetic subjects. Accordingly, the uptake of DiI-labelled oxLDL was increased after exposure to high glucose. Silencing of CD36 abolished the induction of CD36 and reduced the expression of calcification enzymes and mineralization of VSMC. Our results indicate that CD36 signaling is involved in hyperglycemia and oxLDL-induced vascular calcification in diabetes.
REVIEW | doi:10.20944/preprints202311.1097.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Atherosclerosis; psoriasis; microRNA; extracellular vesicles; long non-coding RNA
Online: 17 November 2023 (02:35:39 CET)
It is generally accepted that atherosclerosis is a chronic inflammatory disease. The link between atherosclerosis and other inflammatory diseases such as psoriasis, type 2 diabetes mellitus (T2DM), and rheumatoid arthritis (RA) via metabolic, inflammatory, and immunoregulatory pathways is well established. The aim of our review was to summarize the associations between selected microRNAs (miRs) and long non-coding RNAs (lncRNAs) and atherosclerosis, psoriasis, T2DM, and RA. MicroRNAs are short noncoding RNA molecules involved in cell signaling, intracellular communication, and gene expression. We reviewed the role of miR-146a, miR-210, miR-143, miR-223, miR-126, miR-21, miR-155, miR-145, miR-200, miR-133, miR-135, miR-221, miR-424, and let-7 in atherosclerosis, psoriasis, T2DM, and RA. LncRNAs are RNA transcripts longer than 200 nucleotides that are involved in cellular processes such as apoptosis, metabolism, inflammation, cell differentiation, and proliferation. We evaluated the role of lncRNA-H19, lncRNA-MEG3, lncRNA-UCA1, and lncRNA-XIST in atherosclerosis and psoriasis, T2DM, and RA. Extracellular vesicles (EVs) are a method of intracellular signal transduction. Their function depends on surface expression, cargo, and the cell from which they originate.
ARTICLE | doi:10.20944/preprints202311.0068.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Primary hyperparathyroidism; Plasma atherogenic index; Atherosclerosis; Coronary flow reserve
Online: 1 November 2023 (13:16:23 CET)
Introduction: The coronary flow reserve (CFR) is a sign of early-stage coronary artery disease (CAD). Plasma atherogenic index (PAI) is related to atherosclerosis and cardiovascular mortality. Therefore, our aim was to determine CFR and PAI in patients with primary hyperparathyroidism (PHPT) and investigate whether PAI can be used in the detection of early-stage CAD. Material and Methods: The sample was comprised of 44 patients with PTHT and 33 healthy volunteers. We defined CFR as the ratio of the hyperemic diastolic peak velocity to the baseline diastolic peak velocity. PAI values were calculated with the formula of log 10 triglyceride (TRG) / high-density lipoprotein (HDL). Result: The comparison of the groups for PAI and CFR demonstrated that PAI levels were significantly higher while CFR levels were significantly lower in the PTHT patients (p<0.01, p=0.01, respectively). The correlation analysis revealed that CFR was negatively correlated with PAI and TRG (PAI- p<0.0001 r=-0.537).The multivariate logistic regression analysis showed that only a high PAI level (OR: 151.6, 95% confidence interval (CI): 4.1-5480, p=0.006) was an independent predictor of reduction in CFR in PHPT patients. Conclusion: Overall, we found an independent correlation between PAI and CFR values. Hence, PAI may be useful in identifying PHPT patients facing a high risk of adverse cardiovascular events and may also allow early diagnosis of subclinical atherosclerosis.
REVIEW | doi:10.20944/preprints202309.1893.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: atherosclerosis; coronary artery disease; stent; bio-resorbable; 3D printing
Online: 27 September 2023 (11:23:16 CEST)
Coronary artery disease is the most prevalent cardiovascular disease, claiming millions of lives annually around the world. The current treatment includes surgically inserting a tubular construct called as a stent inside arteries to restore blood flow. However, due to lack of patient-specific design, the commercial products cannot be used with different vessel anatomies. In this review, we have summarized the drawbacks in existing commercial metal stents which face problems of restenosis and inflammatory responses, owing to the development of neointimal hyperplasia. Further, we have highlighted the fabrication of stents using biodegradable polymers, which can circumvent most of the existing limitations. In this regard, we elaborated on utilization of new fabrication methodologies based on additive manufacturing such as three-dimensional printing to design patient-specific stents. Finally, we have discussed on the functionalization of these stent surfaces with suitable bioactive molecules which can prove to enhance their properties in preventing thrombosis and better healing of injured blood vessel lining.
ARTICLE | doi:10.20944/preprints202307.0687.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Shexiang Baoxin Pill; Atherosclerosis; Gut microbiota; Fecal metabolites; Correlation
Online: 11 July 2023 (10:25:05 CEST)
Background: Atherosclerosis (AS), a key pathological contributor of cardiovascular diseases (CVDs), was characterized by formation of atherosclerotic plaque in aortic wall and caused high mortality and morbidity worldwide. Factors contributing to the initiation and progression of AS included vascular endothelial dysfunction, dyslipidemia, inflammation, and oxidative stress. Shexiang Baoxin Pill (SBP) was a traditional Chinese medicine that had been widely applied in clinic and proved to be effective for patients with CVDs. However, the mechanisms underlying its anti-atherosclerotic effects have not been completely elucidated. The study aimed to investigate the protective effects of SBP on AS and its potential mechanisms. Methods: Different dose of SBP was orally administered in apolipoprotein E-deficient (ApoE-/-) mice treated with a high-fat diet (HFD). Histopathological and immunohistochemical analysis, ELISA, untargeted metabolomics analysis, 16S rRNA sequence analysis, and spearman analysis were applied to identify the protective effects and mechanisms of SBP in HFD-induced AS. Results: SBP significantly alleviated HFD-induced atherosclerotic lesion both in aorta and aortic sinus with a reduction in serum levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), as well as interleukin-6 (IL-6) and interleukin-1β (IL-1β), and increased high-density lipoprotein cholesterol (HFD-C) level with no significant change of body weight in HFD-induced ApoE-/- mice. Mechanismly, SBP markedly reshaped the gut microbiota composition and associated metabolomic characteristics. 2 differential intestinal floras at phylum level and 8 differential microbes at genus level, 5 metabolic pathways and 9 differential fecal metabolites related to CVDs were figured out. Besides, intensive correlation between 8 differential microbes and 9 fecal metabolites was observed. Conclusions: Our results showed that SBP could improve HFD-triggered serum lipid disorder, systematic inflammation, and contribute to the alleviation of atherosclerotic lesion. The antiatherogenic properties of SBP might partly result from the reshaping of the gut microbiota and fecal metabolic profile.
ARTICLE | doi:10.20944/preprints202102.0577.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: carotid atherosclerosis; pre-diabetes mellitus; microRNAs; inflammation; metformin therapy
Online: 25 February 2021 (11:43:02 CET)
BACKGROUND AND PURPOSE—Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, the metformin therapy reducing the metabolic distress and the inflammatory burden, could lead to reduction of MACE in ACAS patients with pre-diabetes. In this setting, microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture and worse prognosis in normoglycemics (NG) vs. pre-diabetics metformin users (PDMU) vs. pre-diabetics non metformin users (PDNMU). However, the aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG vs. PDMU vs. PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. METHODS—The study included 234 patients with ACAS divided in NG (n 125), PDNMU (n 73) and PDMU (n 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from plasma samples of the patients from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG vs. PDMU vs. PDNMU. RESULTS—prediabetics vs. NG had over-inflammation (p<0.05) and over expressed miR 24 and miR 27 at baseline. At 2 years of follow-up PDNMU vs. NG, PDMU vs. NG and PDNMU vs. PDMU over-expressed inflammatory markers and miR 24, miR 27, miR 100, miR 126 and miR 133 (p<0.05). Finally, at follow-up end we observed a significant difference about MACE comparing PDNMU vs. NG (n 27 (36.9%) vs. n 8 (6.4%); p<0.05), PDNMU vs. PDMU (n 27 (36.9%) vs. n 6 (16.6%); p <0.05), and PDMU vs. NG (n 6 (16.6%) vs. n 8 (6.4%); p<0.05). Admission glucose values (HR 1.020, CI 95% [1.001-1.038], p 0.029), atheromatous carotid plaque (HR 5.373, CI 95% [1.251-11.079], p 0.024), and miR 24 (HR 3.842, CI 95% [1.768-19.222], p 0.011) predicted MACE at 2 years of follow-up. CONCLUSIONS—Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU vs. PDMU after endarterectomy. MiR24, hyperglycemia and atheromatous plaque could predict MACE at 2 years of follow-up.
REVIEW | doi:10.20944/preprints202008.0119.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: astaxanthin; cardiovascular disease; atherosclerosis; inflammation; oxidative stress; carotenoids; antioxidant
Online: 5 August 2020 (09:53:14 CEST)
Cardiovascular disease is the most common cause of death. Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular diseases, so anti-inflammatory and antioxidant agents that modulate redox balance have become the targets of research to evaluate their molecular mechanisms and therapeutic properties. Astaxanthin, a carotenoid of the xanthophyll group, has potent antioxidant effects due to its molecular structure and its arrangement in the plasma membrane, factors that favor the neutralization of reactive oxygen and nitrogen species. This carotenoid also stands out for its anti-inflammatory activity, possibly interrelated with its antioxidant effect, as well as for its modulation of lipid and glucose metabolism. Considering the potential positive effects of astaxanthin on cardiovascular health evidenced by preclinical and clinical studies, this paper describes the molecular and cellular mechanisms related to the antioxidant and anti-inflammatory properties of this carotenoid in cardiovascular diseases, especially atherosclerosis.
REVIEW | doi:10.20944/preprints202001.0087.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: Chronic stress; Vascular senescence; inflamamtion; atherosclerosis; dipeptidyl peptidase-4
Online: 9 January 2020 (13:05:26 CET)
Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging, angiogenesis, and atherosclerosis-based cardiovascular disease (ACVD). Dipeptidyl peptidase-4 (DPP-4) is a complex enzyme (also called CD26) that acts as a membrane-anchored cell surface exopeptidase. DPP4 is upregulated in metabolic and inflammatory cardiovascular disorders. The widespread expression of DPP4 macrophages and immune cells and the noncatalytic function of DPP4 (also called CD26) as a signaling and binding protein across a wide range of species suggest a teleological role for DPP4 in inflammation and immune response. DPP-4 exhibits many physiological and pharmacological functions by regulating its extremely abundant substrates [e.g., stromal cell-derived factor-1α/ C-X-C chemokine receptor type-4, glucagon-like peptide-1 (GLP-1), etc.]. Over last ten year, emerging data demonstrated unexpected roles for GLP-1 and DPP-4 in extracellular and intracellular signaling, immune activation, inflammation, oxidative stress production, cell apoptosis, insulin resistance, and lipid metabolism,. This mini review has focuses on recent novel findings in this field, highlighting an imbalance between GLP-1 and DPP4 as a potential therapeutic molecular target in treatments of chronic psychological stress-related atherosclerotic cardiovascular disease in humans and animals.
ARTICLE | doi:10.20944/preprints201910.0230.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: carotid intraplaque hemorrhage; carotid atherosclerosis; semi-automatic quantification; MPRAGE
Online: 20 October 2019 (01:39:19 CEST)
Purpose: Carotid intraplaque hemorrhage (IPH) increases risk of territorial cerebral ischemic events, but different sequences or criteria have been used to diagnose or quantify carotid IPH. The purpose of this study was to compare manual segmentation and semi-automatic segmentation for quantification of carotid IPH on magnetization-prepared rapid acquisition with gradient-echo (MPRAGE) sequences. Methods: Forty patients with 16–79% carotid stenosis and IPH on MPRAGE sequences were reviewed by two trained radiologists with more than five years of specialized experience in carotid plaque characterization with carotid plaque MRI. Initially, the radiologists manually viewed the IPH based on the MPRAGE sequence. IPH volume was then measured by three different semi-automatic methods, with high signal intensity 150%, 175%, and 200%, respectively, above that of adjacent muscle on the MPRAGE sequence. Agreement on measurements between manual segmentation and semi-automatic segmentation was assessed using the intraclass correlation coefficient (ICC). Results: There was near-perfect agreement between manual segmentation and the 150% and 175% criteria for semi-automatic segmentation in quantification of IPH volume. The ICC of each semi-automatic segmentation were as follows: 150% criteria: 0.861, 175% criteria: 0.809, 200% criteria: 0.491. The ICC value of manual vs. 150% criteria and manual vs. 175% criteria were significantly better than the manual vs. 200% criteria (p < 0.001). Conclusions: The ICC of 150% and 175% criteria for semi-automatic segmentation are more reliable for quantification of IPH volume. Semi-automatic classification tools may be beneficial in large-scale multicenter studies by reducing image analysis time and avoiding bias between human reviewers.
ARTICLE | doi:10.20944/preprints201810.0766.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Nuclear transcription, endothelium, atherosclerosis, serum amyloid A, vascular function
Online: 2 November 2018 (14:04:15 CET)
The acute phase protein serum amyloid A (SAA) is associated with endothelial dysfunction and early-stage atherogenesis. Stimulation of vascular cells with SAA increases gene expression of pro-inflammation cytokines and tissue factor (TF). Activation of the transcription factor, nuclear factor kappa-B (NFkB), may be central to SAA-mediated endothelial cell inflammation, dysfunction and pro-thrombotic responses, while targeting NFkB with a pharmacologic inhibitor, BAY11-7082, may mitigate SAA activity. Human carotid artery endothelial cells (HCtAEC) were pre-incubated (1.5 h) with 10 µM BAY11-7082 or vehicle (control) followed by SAA (10 μg/mL; 4.5 h). Under these conditions gene expression for TF and TNF increased in SAA-treated HCtAEC and pre-treatment with BAY11-7082 significantly (TNF) and marginally (TF) reduced mRNA expression. Intracellular TNF and IL-6 protein also increased in HCtAEC supplemented with SAA and this expression was inhibited by BAY11-7082. Supplemented BAY11-7082 also significantly decreased SAA-mediated leukocyte adhesion to apolipoprotein E-deficient mouse aorta in ex vivo vascular flow studies. In vascular function studies, isolated aortic rings pre-treated with BAY11-7082 prior to incubation with SAA showed improved endothelium-dependent vasorelaxation and increased vascular cGMP content. Together these data suggest that inhibition of NFkB activation may protect endothelial function by inhibiting the pro-inflammatory and pro-thrombotic activities of SAA.
REVIEW | doi:10.20944/preprints201705.0019.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: surrounding microRNAs; low-density lipoprotein; atherosclerosis; APOB; PCSK9; LDLR
Online: 1 May 2017 (11:30:17 CEST)
The atherosclerosis, a chronic and inflammatory disease that occurs when there are high levels of low-density lipoprotein (LDL) on plasma. This important risk factor for development of cardiovascular disease (CVD) is the main cause of death worldwide. MicroRNAs have recently emerged as potential biomarkers and therapeutic target for lipid metabolism disorders. In this review, we will provide profile of surrounding miRNAs that have demonstrated being regulators of PCSK9, LDLR and APOB100 genes. Recent work has identified the mir-148, mir-128, mir-27a/b, mir-185, mir-301, mir-130 as important regulators of this pathway because they decrease supply of LDL receptors through interaction with PCSK9. Inhibition of LDLR expression cause elevation of plasma LDL levels which induces atherosclerosis. While mir-30c, mir-122, mir-34 decrease MTTP, which promotes degradation of APOB100 preventing assembly and secretion of VLDL. We conclude that, when overexpressed, mir-148a, mir128 and mir-27a/b, mir-122 and mir-34 are related to decrease in LDLR, facilitating occurrence of atherosclerosis. While mir-30 has been linked to decreased atherosclerosis. Detection of miRNAs profile could be used in the future as a biomarker for disturbs linked to c-LDL uptake and in future anti-miRNAs therapies may be used in the treatment of atherosclerosis.
ARTICLE | doi:10.20944/preprints202309.1424.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: dabigatran etexilate; exercise training; atherosclerosis; plaque stability; matrix metalloproteinases; inflammation
Online: 21 September 2023 (07:36:12 CEST)
Aim: Complementary effects of dabigatran etexilate (DE), exercise training (ET) and combination (DE+ET) on the development and composition of the atherosclerotic lesions in diabetic apoE knockout (apoE-/-) mice. Methods: In 48 male apoE-/- diabetic mice, streptozotocin (STZ) was induced for 5 consecutive days. Mice received figh-fat diet (HFD) for 8 weeks and were randomized into 4 groups (1.Control/CG, 2.DEG: HFD with DE, 3.ETG: ET on treadmill, 4.DE+ETG: Combination DE and ET treatment). At the end of 8th week, all mice were euthanatized and morphometry of the aortic lesions at the level of aortic valve was obtained. Collagen, elastin, TNF-a, MCP-1, matrix-metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentration within plaques at aortic valve were determined. Results: All active groups had significantly smaller aorta stenosis (DEG:7.9±2.2%, ETG:17.3±5.3%, DE+ETG:7.1±2.7%) compared to CG (23.3±5.5% p<0.05), reduced the relative intra-plaque concentrations of macrophages, MCP-1, MMP-3 and MMP-9, and considerably increased collagen, elastin and TIMP-1 (p<0.05). Group 4 showed the most pronounced results (p<0.05). Both DEG and DE+ETG significantly reduced MMP-2 and TNF-a concentrations compared to ETG and CG (p<0.010). Conclusion: DE and ET treatment in diabetic apoE-/- mice showed complementary amelioration of atherosclerotic lesions development and stability, mediated by the anti-inflammatory modulation of both DE and ET.
REVIEW | doi:10.20944/preprints202307.1210.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Peripheral arterial diseases; Somatic mutation; Thrombosis; Atherosclerosis; Inflammation; Genetic disorders
Online: 18 July 2023 (10:13:12 CEST)
Peripheral arterial diseases (PAD) are complex cardiovascular conditions influenced by environmental factors and somatic mutations in multiple genes involved in hematopoiesis and inflammation. While traditional risk factors such as smoking, hypercholesterolemia, and hypertension have been extensively studied, the role of somatic mutations in PAD progression remains underexplored. This article aims to provide a comprehensive review of the molecular mechanisms, genetic landscape, prognostic significance, and clinical implications of somatic mutations in PAD. The expansion of clonal hematopoiesis of indeterminate potential (CHIP) clones in the circulating blood, named clonal hematopoiesis (CH), leads to the infiltration of these clones into atherosclerotic plaques and the production of inflammatory cytokines, increasing the risk of cardiovascular diseases including PAD. Furthermore, recent experimental evidence has demonstrated the involvement of somatically mutated TP53 genes with a high variant allele frequency (VAF) in PAD development and prognosis. The review delves into the relationship between CH and PAD, elucidating the prevalence, impact, and underlying mechanisms of this association. This understanding paves the way for novel therapeutic approaches targeting CHIP to promote tissue regeneration and improve outcomes in PAD patients. It emphasizes the need for further re-search to fully unravel the genetic footprint of the disease and highlights potential clinical implications. The findings presented in this article lay the foundation for personalized medicine approaches and open avenues for the development of targeted therapies based on somatic mutation profiling.
REVIEW | doi:10.20944/preprints202306.2222.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Gut microbiota; Cardiovascular diseases; Trimethylamine N-Oxide; Heart failure; Atherosclerosis
Online: 30 June 2023 (11:58:11 CEST)
Much evidence reveals an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these, the most important is the Trimethylamine N-Oxide (TMAO), which is responsible through various mechanisms for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with HF, and the possible strategies to influence its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and new therapeutic target of HF.
REVIEW | doi:10.20944/preprints202306.1863.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: atherosclerosis; stroke; carotid; stenosis; biomarker; plaque; lipid; inflammation; IL-6
Online: 27 June 2023 (11:00:33 CEST)
Intracranial and extracranial large artery atherosclerosis (LAA) are a main cause of ischemic stroke. Biomarkers may aid in the diagnosis of LAA and help to stratify patients´ risk of stroke. We performed a narrative review of the literature mainly published in the last five years with the aim of identifying biomarkers associated either with intracranial or extracranial LAA in humans. Several potential biomarkers of LAA mainly related to lipid pathways and inflammation have been studied. Diagnostic biomarkers of LAA were evaluated by measuring biomarkers levels in patients with LAA stroke and other stroke etiologies. Some biomarkers were associated with prognosis of LAA stroke as evaluated by the modified Rankin score. Increased levels of IL-6 and have been associated with the risk of progression of the atherosclerotic disease. Overall, in most studies, the results were not externally validated. External validation of these results is needed. In the future, biomarkers could be useful for the selection of patients for clinical trials. To adopt these biomarkers in clinical practice we will need robust multicentric studies proving their reproduci-bility and a clear practical applicability for their use.
REVIEW | doi:10.20944/preprints201806.0239.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: ApoB-100 lipoproteins-Proteoglycans-Interactions-Arterial intima Atherosclerosis-LDL modifications
Online: 14 June 2018 (16:17:40 CEST)
Experimental and clinical data indicates that the initiation and progress of atherosclerosis, and its clinical manifestations, are caused first by circulating apoB-100 lipoproteins that enter and are retained in the arterial intima. Extracellular sulfated proteoglycans (PGs) of the intima are the retention agents. The PGs also initiate physical and biochemical lipoprotein degradation with the production of bioactive, lipid products that trigger an inflammatory response that leads to atherosclerosis. There are many simple methods for measuring abnormalities of circulating lipoproteins and their relation to atherosclerotic cardiovascular disease (ACVD). However, limited research has been aimed to evaluate procedures that could report quantitatively about the contribution of the apo-100 lipoprotein-arterial intima PGs interaction to clinical manifestation of ACVD. In the present review we will discuss observations indicating that simple ex vivo evaluation of the affinity of apoB-100 lipoproteins for arterial PGs and glycosaminoglycans (GAGs) can give indication of its association with clinical manifestations of atherosclerosis. In addition, we will discuss molecular and cellular aspect of the apoB-100 lipoproteins association with arterial PGs that are related to atherogenesis and that support the experimental framework behind the current “Response-to-Retention” hypothesis of atherosclerosis
REVIEW | doi:10.20944/preprints201711.0038.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: phospholipids; atherosclerosis; inflammation; anti-inflammatory; dairy; marine; meat; egg; nutrition
Online: 6 November 2017 (10:30:12 CET)
In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been critically appraised and evaluated. The paper is divided into three sections: Section one addresses the relationship between the anti-inflammatory bioactivities of different phospholipids in relation to their structures and compositions. Sections two and three are dedicated to the structures, functions and anti-inflammatory properties of dietary phospholipids from animal and marine sources. Most of the dietary phospholipids of animal origin come from meat, egg and dairy products. To date, there is very limited work published on meat phospholipids, undoubtedly due to the negative perception that meat consumption is an unhealthy option due to its putative associations with several chronic diseases. These assumptions are addressed with respect to the phospholipid composition of meat products. Recent research trends indicate that dairy phospholipids possess anti-inflammatory properties, which has led to an increased interest into their molecular structures and reputed health benefits. Finally, the structural composition of phospholipids of marine origin is discussed. Extensive research has been published in relation to ω-3 polyunsaturated fatty acids (PUFAs) and inflammation, however this research has recently come under scrutiny and has proved to be unreliable and controversial in terms of the therapeutic effects of ω-3 PUFA, which are generally in the form of triglycerides and esters. Therefore, this review focuses on recent publications concerning marine phospholipids and their structural composition and related health benefits. Finally, the strong nutritional value of dietary phospholipids are highlighted with respect to marine and animal origin and avenues for future research are discussed.
REVIEW | doi:10.20944/preprints202311.0217.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Thromboinflammation; atherosclerosis; neutrophil extracellular traps; NETosis; von Willebrand Factor; neutrophil inflammasome
Online: 3 November 2023 (11:17:35 CET)
The interplay between thrombosis and inflammation, known as thromboinflammation, is a significant pathway driving cardiovascular and autoimmune diseases, as well as COVID-19. Key modulators of this process have emerged as innate immune cells. Strategically positioned to promote thromboinflammation are neutrophils, the most predominant white blood cells in humans. Neutrophils can trigger an organized cell death pathway by releasing decondensed chromatin structures known as neutrophil extracellular traps. These structures are decorated with histones, cytoplasmic, and granular proteins, and have cytotoxic, immunogenic, and prothrombotic effects, which can accelerate disease progression. The activities of PAD4, which catalyses the citrullination of histones, and the neutrophil inflammasome are required for distinct steps leading to extracellular DNA release (NETosis). PAD4 activity has important implications for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. We will discuss how vascular blockages in thromboinflammation occur due to the interaction between neutrophil extracellular traps and ultra-large VWF (von Willebrand Factor). PAD4 activity has important implications for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. It will also review the mechanisms whereby vaso-occlusive events in thrombo-inflammation depend on the interaction of neutrophil extracellular traps with von Willebrand factor and suggest the importance of PAD4 in neutrophil inflammasome assembly and neutrophil extracellular traps in thrombo-inflammatory diseases such as atherosclerosis and CVD.
COMMUNICATION | doi:10.20944/preprints202307.1930.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: CETP; atherosclerosis; inflammation; macrophages; nicotinamide nucleotide transhydrogenase; LDL receptor knockout mice
Online: 27 July 2023 (13:38:57 CEST)
CETP activity reduces plasma HDL-cholesterol concentrations, a correlate of increased risk of atherosclerotic events. However, our recent findings suggest that CETP expression in macrophages promotes an intracellular antioxidant state, reduces free cholesterol accumulation and phagocytosis, and attenuates pro-inflammatory gene expression. To determine whether CETP expression in macrophages affects atherosclerosis development, we transplanted bone marrow from transgenic mice expressing simian CETP or non-expressing littermates into hypercholesterolemic LDL receptor deficient mice. CETP expression did not change lipid-stained lesion areas but decreased macrophage content (CD68), neutrophil accumulation (LY6G) and aorta content of young male transplanted mice and decreased LY6G, TNF-α, iNOS and nitrotyrosine (3-NT) in aged female transplanted mice. These findings suggest that CETP expression in bone marrow-derived cells reduces inflammatory features of atherosclerosis. These novel mechanistic observations may help explain the failure of CETP inhibitors to reduce atherosclerotic events in humans.
REVIEW | doi:10.20944/preprints202008.0457.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: cardiovascular disease; hypertension; atherosclerosis; electroneutral transport; cation-chloride-cotransporters; KCCs; NKCCs
Online: 20 August 2020 (13:00:59 CEST)
The SLC12 family of cation-chloride-cotransporters (CCCs), comprising potassium chloride cotransporters (KCCs)-mediated Cl- extrusion relative to sodium chloride cotransporters (NKCCs)-mediated Cl- loading, play vital roles in cell volume regulation and ion homeostasis. These functions of the CCCs influence a variety of physiological processes, many of which overlap with the pathophysiology of cardiovascular disease. Although not all of the cotransporters have been linked to Mendelian genetic disorders, recent studies have provided new insights into their functional role in vascular and renal cells along with their contribution to cardiovascular diseases. Particularly, an imbalance in potassium levels promote the pathogenesis of atherosclerosis and disturbances in sodium homeostasis are one of the causes of hypertension. Recent findings even suggest hypothalamic signalling as a key signalling pathway in the pathophysiology of hypertension. In this review, we summarize and discuss the role of CCCs in cardiovascular disease with particular emphasis on knowledge gained in recent years on NKCCs and KCCs.
REVIEW | doi:10.20944/preprints202004.0430.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: atherosclerosis; sars-cov-2; covid-19; pathogenesis of sars-cov-2
Online: 24 April 2020 (08:58:13 CEST)
Sars-CoV-2 outbreak represents a public health emergency, affecting different regions of the world. Lung is the organ more damaged due to the high presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection vary from absence of symptomatology to be more severe, characterized by acute respiratory distress syndrome (ARDS), multiorgan failure and sepsis requiring treatment in Intensive Care Unit (ICU).It is not still clear why in a small percentage of patients immune system is not able to efficiently suppress viral replication. It has been documented as predictive factors for severity and susceptibility affections of cardiovascular system such as heart failure (HF), coronary heart disease (CHD) and risk factors for atherosclerotic progression, hypertension and diabetes among others.Atherosclerotic progression, as chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory pattern, including (Interleukin 6) IL-6, Tumor Necrosis Factor α (TNF-α) and IL-1β raise. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results report in severe Sars-CoV-2 infection we have supposed a pathogenetic correlation. Atherosclerosis may be a pathogenetic ideal substrate to high viral replication ability leading to adverse outcomes, how reported in patients with cardiovascular factors. Moreover, level of atherosclerotic progression may impact on a different degree of severe infection and in a vicious circle feeding itself Sars-CoV-2 may exacerbate atherosclerotic progression due to excessive and aberrant plasmatic concentration of cytokines.
REVIEW | doi:10.20944/preprints202308.1889.v1
Subject: Biology And Life Sciences, Biophysics Keywords: cholesterol homeostasis; cardiac remodeling; inflammation; atherosclerotic; cardiomyocytes; atherosclerosis; catabolic and anabolic pathways
Online: 29 August 2023 (03:39:04 CEST)
The metabolism of lipoproteins, which regulates the transit of the lipid to and from tissues, is crucial to maintaining cholesterol homeostasis. Cardiac remodeling is referred to as a set of molecular, cellular, and interstitial changes that, following injury, affect the size, shape, function, mass, and geometry of the heart. Acetyl coenzyme A (acetyl CoA), which can be made from glucose, amino acids, or fatty acids, is the precursor for the synthesis of cholesterol. In this article, authors explain concepts behind cardiac remodeling, its clinical ramifications, and the pathophysiological roles played by numerous various components, such as cell death, neurohormonal activation, oxidative stress, contractile proteins, energy metabolism, collagen, calcium transport, inflammation, and geometry. The levels of cholesterol are traditionally regulated by two biological mechanisms at the transcriptional stage. First, the SREBP transcription factor family regulates the transcription of crucial rate-limiting cholesterogenic and lipogenic proteins, which in turn limits cholesterol production. Immune cells become activated, differentiated, and divided, during an immune response with the objective of eradicating the danger signal. In addition to creating ATP, which is used as energy, this process relies on metabolic reprogramming of both catabolic and anabolic pathways to create metabolites that play a crucial role in regulating the response. Because of changes in signal transduction, malfunction of the sarcoplasmic reticulum and sarcolemma, impairment of calcium handling, increases in cardiac fibrosis, and progressive loss of cardiomyocytes, oxidative stress appears to be the primary mechanism that causes the transition from cardiac hypertrophy to heart failure. De novo cholesterol production, intestinal cholesterol absorption, and biliary cholesterol output are consequently crucial processes in cholesterol homeostasis. In the article's final section, the pharmacological management of cardiac remodeling is explored. The route of treatment is explained into different steps: including, promising, and potential strategies. This chapter offers a brief overview of the history of the study of cholesterol absorption as well as the different potential therapeutic targets.
REVIEW | doi:10.20944/preprints202308.0277.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: lipoproteins; atherosclerosis; dyslipidaemia; apolipoprotein B; residual risk; triglyceride-rich lipoprotein; remnant lipoprotein
Online: 3 August 2023 (05:43:34 CEST)
Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide and the risk of a major cardiovascular event is highest among those with established disease. Ongoing management of these patients relies on the accurate assessment of their response to any prescribed therapy, and their residual risk, in order to optimize treatment. Recent international guidelines and position statements concur that the plasma concentration of apolipoprotein B (apoB) is the most accurate measure of lipoprotein associated ASCVD risk. This is especially true for the growing number of individuals with diabetes, obesity or the metabolic syndrome, and those on statin therapy. Most guidelines, however, continue to promote LDL-C as the primary risk marker due to uncertainty as to whether the greater accuracy of apoB is sufficient to warrant a paradigm shift. Recommendations regarding apoB measurement vary, and the information provided on how to interpret apoB results is sometimes insufficient, particularly for the non-lipid specialist. Misinformation regarding the reliability of the assays is also frequently repeated despite its equivalent or better standardization than many other diagnostic assays. Thus, demand for apoB testing is relatively low, which means there is little incentive to increase its availability or reduce its cost. In this review, we examine the results of recent clinical outcomes studies and meta-analyses on the relative values of apoB, LDL-C and non-HDL-C as markers of ASCVD risk. Although there is seemingly minimal difference among these markers when only population-based metrics are considered, it is evident from our analysis that, from a personalized or precision medicine standpoint, a great many individuals would benefit, at a negligible total cost, if apoB measurement were better integrated into the diagnosis and treatment of ASCVD.
ARTICLE | doi:10.20944/preprints202305.1292.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Carotid atherosclerosis [C10,228,140,300,200]; cardiovascular risk factors [E05,318,740,600,800,725,500,500]; carotid intima-media thickness [E01,370,350,850,150]
Online: 18 May 2023 (07:52:00 CEST)
Introdução: Os fatores de risco vasculares são decisivos na evolução da doença aterosclerótica e a ecografia Doppler carotídea e vertebral permite acompanhar o seu aparecimento e evolução. A medida do espessamento da parede arterial permite o diagnóstico precoce da doença potencializando seu tratamento e controle dos fatores de risco vasculares. Objetivo: Analisar a presença de doença ateromatosa em indivíduos com idade > 65 anos e compreender sua transformação com fatores de risco vascular. Materiais e Métodos: Estudo observacional transversal, em indivíduos com idade > 65 anos manifestados ao ecoDoppler carotídeo entre 1º de janeiro de 2012 e 31 de dezembro de 2021. Foi calculado o índice médio-intimal, a presença de placas ateromatosas, sua repercussão hemodinâmica e fatores de risco vascular foram registrados. Resultados: Obteve-se uma amostra de 5885 indivíduos, sendo 41,8% do sexo feminino e 58,2% do sexo masculino. A média de idade foi de 76,59 anos, variando entre 65 e 98 anos (+6,69). A hipertensão arterial foi a mais prevalente 81,3%. Houve relação positiva significativa entre índice médio-intimal, idade e história pessoal de doenças cardiovasculares e cerebrovasculares (p=0,001). Na presença de placas, sexo masculino, hipertensão arterial, diabetes, dislipidemia, tabagismo e história pessoal de doenças cardiovasculares e cerebrovasculares apresentadas de forma positiva. Conclusões: Nesta amostra, fatores de risco vascular não modificáveis parecem ser determinantes na presença de aumento da espessura da parede arterial. Na presença de sinais de um estágio mais avançado da doença aterosclerótica, os fatores de risco vascular modificáveis são decisivos,
ARTICLE | doi:10.20944/preprints202301.0160.v1
Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: Intermittent fasting; glucose tolerance; hepatic steatosis; adipose tissue; reverse cholesterol transport; atherosclerosis.
Online: 9 January 2023 (10:49:54 CET)
In humans and animal models, intermittent fasting (IF) interventions promote body weight loss, improve metabolic health, and are thought to lower cardiovascular disease risk. However, there is a paucity of reports on the relevancy of such nutritional interventions in the context of dyslipidemia and atherosclerotic cardiovascular diseases. The present study assessed the metabolic and atheroprotective effects of intermittent fasting intervention (IF) in atherosclerosis-prone apolipoprotein E-deficient (Apoe-/-) mice. Groups of male and female Apoe-/- mice were fed a regular (chow) or atherogenic (high-fat, high-cholesterol, HFCD) diet for 4 months, either ad libitum or in an alternate-day fasting manner. The results show that IF intervention improved glucose and lipid metabolism independently of sex. However, IF only decreased body weight gain in males fed chow diet and differentially modulated adipose tissue parameters and liver steatosis in a diet composition-dependent manner. Finally, IF prevented spontaneous aortic atherosclerotic lesions formation in mice fed chow diet, irrespective of sex but failed to reduce HFCD-diet-induced atherosclerosis. Overall, the current work indicates that IF interventions can efficiently improve glucose homeostasis and treat atherogenic dyslipidemia, but a degree of caution is warranted with regard to the individual sex and the composition of the dietary regimen.
REVIEW | doi:10.20944/preprints202201.0241.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Diabetes Mellitus; Vascular Dementia; Alzheimer’s Disease; Inflammation; Atherosclerosis; Mitochondrial dysfunction; Cognitive dysfunction
Online: 17 January 2022 (15:46:10 CET)
Type 2 Diabetes Mellitus is being increasingly associated with dysfunction of cognition. Dementia, including vascular dementia and Alzheimer’s disease, is being recognized as comorbidities of this metabolic disorder. The progressive hallmarks of this cognitive dysfunction include mild impairment of cognition and cognitive decline. Dementia and mild impairment of cognition appear in older patients primarily. Studies on risk factors, neuropathology, and brain imaging have provided important suggestions for mechanisms that lie behind the development of dementia. It is a significant challenge to understand the disease processes related to diabetes which affect the brain and lead to dementia development. The connection between Diabetes Mellitus and dysfunction of cognition has been observed in many human and animal studies that have noted mechanisms related to Diabetes Mellitus are possibly responsible for aggravating cognitive dysfunction. This article attempts to narrate the possible association between type 2 diabetes and Dementia, reviewing studies that have noted this association in vascular dementia and Alzheimer’s disease and helping to explain the potential mechanisms behind the disease process. The Google search for ‘Diabetes Mellitus and Dementia’ was carried out. Also, the search was done using ‘Diabetes Mellitus,’ ‘Vascular Dementia,’ ‘Alzheimer’s Disease.’ The literature search was done from Google Scholar, Pubmed, Embase, ScienceDirect, and MEDLINE. Keeping in mind the increasing rate of Diabetes Mellitus, it is important to establish the type 2 diabetes effect on the brain and diseases of neurodegeneration. This narrative review aims to build awareness regarding different types of dementia and their relationship with diabetes.
REVIEW | doi:10.20944/preprints202111.0300.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Endocrine disruptors; gender; female; atherosclerosis; Cadmium; Bisphenol A; inflammatory cytokines; cardiovascular diseases
Online: 17 November 2021 (10:53:12 CET)
The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, that could facilitate the development of interventions contributing to “successful aging” and improvement of quality of life. Cardio-vascular diseases (CVD) include pathologies affecting heart or blood vessels, such as hyperten-sion, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations raising the risk of CVD development. Several factors have been claimed to play a role in the alterations observed in muscle and endothelial cells and leading to increased CVD, such as genetic pattern, smoking, unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the last decades attention has been focused on a potential role of several pollutants which disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatic process and CVD progression.
REVIEW | doi:10.20944/preprints202204.0291.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: purinergic signaling; endothelial cells; shear stress; vasodilatation; transcytosis; intimal hyperplasia; atherosclerosis; high-density lipoprotein
Online: 29 April 2022 (08:06:19 CEST)
The endothelium plays a key role in blood vessel health. At the interface of the blood, it releases several mediators that regulate local processes and that protect against the development of cardiovascular disease. In this interplay, there is increasing evidence for a role of extracellular nucleotides and endothelial purinergic P2Y receptors (P2Y-R) in vascular protection. Recent advances have revealed that endothelial P2Y1-R and P2Y2-R mediate nitric oxide-dependent vasorelaxation as well as endothelial cell proliferation and migration, which are processes involved in the regeneration of damaged endothelium. However, endothelial P2Y2-R, and possibly P2Y1-R, have also been reported to promote vascular inflammation and atheroma development in mouse models, with endothelial P2Y2-R also being described as promoting vascular remodeling and neointimal hyperplasia. Interestingly, at the interface with lipid metabolism, P2Y12-R has been found to trigger HDL transcytosis through endothelial cells, a process known to be protective against lipid deposition in the vascular wall. Better characterization of the role of purinergic P2Y-R and downstream signaling pathways in determination of the endothelial cell phenotype in healthy and pathological environments has clinical potential for the prevention and treatment of cardiovascular diseases.
REVIEW | doi:10.20944/preprints202204.0057.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: atherosclerosis; biomechanics; border detection; coronary artery disease; optical coherence to-mography; stents; vulnerable plaque
Online: 7 April 2022 (08:13:34 CEST)
Coronary optical coherence tomography (OCT) is an intravascular, near-infrared light-based imaging modality capable of reaching axial resolutions of 10-20 µm. This resolution allows for accurate determination of high-risk plaque features, such as thin cap fibroatheroma; however, visualisation of morphological features alone still provides unreliable positive predictive capability for plaque progression or future major adverse cardiovascular events (MACE). Biomechanical simulation could assist in this prediction, but this requires extracting morphological features from intravascular imaging to construct accurate three-dimensional simulations of patients’ arteries. Extracting these features is a laborious process, often carried out manually by trained experts. To address this challenge, numerous techniques have emerged to automate these processes while simultaneously overcoming difficulties associated with OCT imaging, such as its limited penetration depth. This systematic review summarises advances in automated segmentation techniques from the past five years (2016-2021) with a focus on their application to the three-dimensional reconstruction of vessels and their subsequent simulation. We discuss four categories based on the feature being processed, namely: coronary lumen; plaque characteristics and subtypes; artery layers; and stents. Areas for future innovation are also discussed as well as their potential for future translation.
REVIEW | doi:10.20944/preprints202111.0175.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: atherosclerotic cardiovascular disease (ACVD); atherosclerosis; gut dysbiosis; immune system; gut microbial metabolites; SCFAs; TMAO
Online: 9 November 2021 (13:45:20 CET)
Atherosclerosis is a leading cause of cardiovascular disease and mortality worldwide. Alterations in the gut microbiota composition, known as gut dysbiosis, have been shown to contribute to atherosclerotic cardiovascular disease (ACVD) development through several pathways. Disruptions in gut homeostasis are associated with activation of immune processes and systemic inflammation. The gut microbiota produces several metabolic products, namely trimethylamine (TMA), which is used to produce the proatherogenic metabolite trimethylamine-N-oxide (TMAO). Short chain fatty acids (SCFAs), including acetate, butyrate, and propionate, and certain bile acids (BAs) produced by the gut microbiota lead to inflammation resolution and decrease atherogenesis. Chronic low-grade inflammation is associated to common risk factors for atherosclerosis, including metabolic syndrome, type 2 diabetes mellitus (T2DM), and obesity. Novel strategies for reducing ACVD include the use of nutraceuticals such as resveratrol, modification of glucagon-like peptide 1 (GLP-1) levels, supplementation with probiotics, and administration of prebiotic SCFAs and BAs. Investigation into the relationship between the gut microbiota and its metabolites, and the host immune system could reveal promising insight into ACVD development, prognostic factors, and treatments.
REVIEW | doi:10.20944/preprints201804.0051.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: atherosclerosis; cardiovascular disease; chaos theory; non-coding RNAs; Alu-elements; NF-κB; miRNA; miRNA sponges
Online: 4 April 2018 (06:36:55 CEST)
Atherosclerosis (ATH) and Coronary Artery Disease (CAD) are chronic inflammatory diseases with an important genetic background which derive from the cumulative effect of multiple common risk alleles, most of them located in genomic non-coding regions. These complex diseases behave as non-linear dynamical systems that show a high dependence on their initial conditions, so that long-term predictions of disease progression are unreliable. One likely possibility is that the non-linear nature of ATH could be dependent on non-linear correlations in the structure of the human genome. In this review we show how Chaos theory analysis highlighted genomic regions that shared specific structural constraints that could have a role in ATH progression. These regions were shown to be enriched in repetitive sequences of the Alu family, genomic parasites which colonized the human genome, which show a particular secondary structure and have been involved in the regulation of gene expression. We also review the impact of Alu elements on the mechanisms that regulate gene expression, especially highlighting the molecular mechanisms by which the Alu elements could alter the inflammatory homeostasis. We devise especial attention to their relationship with the lncRNA ANRIL, the strongest risk factor for ATH, their role as miRNA sponges, and their ability to interfere with the regulatory circuitry of the NF-kB response. We aim to characterize ATH as a non-linear dynamic system in which small initial alterations in the expression of a number of repetitive elements are somehow amplified to reach phenotypic significance.
REVIEW | doi:10.20944/preprints202212.0296.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: atherosclerosis; COVID-19; inflammation; cardiovascular system; cytokines; endothelium; lipoproteins; renin-angiotensin system; atheroma; autoimmunity; vasa vasorum.
Online: 16 December 2022 (06:32:21 CET)
The article describes how atherosclerosis and coronavirus disease 19 (COVID-19) may affect each other. The features of this comorbid pathogenesis at various levels (vascular, cellular and molecular) are considered. A bidirectional influence of these conditions is described: the presence of cardiovascular diseases affects different individual susceptibility to viral infection. In turn, SARS-CoV-2 can have a negative effect on the endothelium and cardiomyocytes, causing blood clotting, secretion of pro-inflammatory cytokines, and thus exacerbating the development of atherosclerosis. In addition to the established entry into cells via ACE2 принимая во внимание его влияние на, other mechanisms of SARS-CoV-2 entry are currently under investigation, for example, through CD147. Pathogenesis of comorbidity can be determined by the influence of the virus on various links which are meaningful for atherogenesis: generation of oxidized forms of LDL, launch of a cytokine storm, damage to the endothelial glycocalyx, and mitochondrial injury. The transformation of a stable plaque into an unstable one plays an important role in the pathogenesis of atherosclerosis complications and can be triggered by COVID-19. The impact of SARS-CoV-2 on large vessels such as aorta is more complex than previously thought considering its impact on vasa vasorum. Current information on the mutual influence of the medicines used in the treatment of atherosclerosis and acute COVID-19 is briefly summarized
ARTICLE | doi:10.20944/preprints202112.0073.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: MicroRNAs; miR-126; mir-197; mir-223; Cardiometabolic Disease; Diabetes; Cardiovascular disease; Atherosclerosis; Inter Media Thickness
Online: 6 December 2021 (12:52:25 CET)
We aim to investigate if serum levels of microRNAs: miR-126, mir-197 and mir-223, previously implicated in cardiometabolic disease, are reproducibly associated with incident-diabetes (inc-DM), incident-cardiovascular disease (inc-CVD) and with carotid atherosclerosis (measured for the maximum thickness of the intima-media of the carotid bulb (IMT)). The microRNAs were measured, one: in serum of 553 subjects from the baseline exam of the Swedish prospective cohort, Malmö Diet and Cancer Study (MDC-CC), with 169 subjects who developed CVD and 140 DM (16 years follow-up) and, two: in 1221 subjects from the Malmö Offspring Study (MOS), with 14 de-veloped CVD and 12 DM (3.7 years follow-up). Multivariate logistic and linear regression models were used to investigate the relationship of serum-concentrations of the microRNAs and inc-DM, inc-CVD, IMT-bulb respectively. In MDC-CC, miR-126 showed significant positive association with inc-DM (p= 0.01) whereas in fully adjusted model, the association was borderline significant (p= 0.05). The results were not replicated in MOS. There was no consistent significant association between the microRNAs with IMT or inc-CVD in any cohort. Our results do not support previous reports on significant associations between these microRNAs and the risk of CMD, as they were not reproducible in our cohorts. In addition, the directionality of any associations found were not consistent with those previously reported.
ARTICLE | doi:10.20944/preprints201908.0300.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: coronary dimensions; Poiseuille’s Equation; arteriovenous fistula; coronary dilatation; wall shear stress; coronary blood flow; atherosclerosis; angiogenesis
Online: 29 August 2019 (03:35:08 CEST)
Background: The purpose was to develop a novel hypothetical method to increase the size of coronary arteries. Methods: In the long-term observation the coronary sizes were dilated in three unexpected scenarios. The coronary artery sizes were observed in patients with mitral stenosis (n=59) by angiogram prior to percutaneous balloon mitral valvuloplasty or valve replacement surgery for severe mitral stenosis. The coronaries of patients with patent ductus arteriosus who underwent surgical closure in the past (n=12) were examined by echocardiogram. Patients with renal failure on long-term dialysis through peripheral arterio-venous fistula without left ventricular hypertrophy (n=17) were studied by echocardiography. Normal age, weight and sex matched coronary sizes served as controls in the study. All these observations were made over a period of 11.5 years. Results: The sizes of coronaries in patients with mitral stenosis, patients who underwent closure for patent ductus arteriosus, and in patients on hemodialysis through arteriovenous fistulas were higher than normal controls (p<0.05, for all). A hypothetical model to increase the coronary sizes could be developed based on the analysis of the differential equations of Poiseuille’s. The proposed method is creating a peripheral arterio-venous fistula, which could be closed later electively by a percutaneous method/surgery. The closure time needs to be determined by experimental studies. The other methods could be a continuous exercise program or usage of beta-blockers. Conclusion: A novel hypothetical method of peripheral arteriovenous fistula formation could potentially increase the size of the coronaries, and this could be closed later.
REVIEW | doi:10.20944/preprints201712.0186.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: cardiovascular diseases; atherosclerosis; oxidative stress; angiogenesis and arteriogenesis; endothelial dysfunction; growth hormone; IGF-I; wound healing
Online: 26 December 2017 (10:30:09 CET)
This review describes the positive effects of growth hormone on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on the vascular endothelium improving its dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease inducing the generation of new collateral vessels able to bypass a major artery occlusion. We include some preliminary data from a trial in which GH or placebo is given to elder people suffering from critical limb ischemia, showing the effects of the hormone on plasma markers of inflammation, and stating that the administration of GH in short periods of time is safe and effective even in diabetic patients. We also analyze how Klotho may have strong relationships with GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH to repair the damaged tissue. Lastly, we show how GH induces wound healing by increasing the blood flow to the ischemic tissue. In summary, we postulate that short-time GH administration is useful for treating cardiovascular diseases.
ARTICLE | doi:10.20944/preprints202306.0867.v1
Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: Sex differences; Chronic Kidney Disease; Atherosclerosis; Foam Cells; Parietal Epithelial Cells (PECs); Angiotensin-Converting Enzyme Inhibitors (ACEi)
Online: 13 June 2023 (03:22:47 CEST)
Background: This study analyzes sex-based differences in renal structure and response to the Angiotensin-Converting Enzyme (ACE) inhibitor enalapril in a mouse model of atherosclerosis. Methods: ApoE-/- mice (8 weeks old) received enalapril (5 mg/kg/day, subcutaneous) or PBS as a control for an additional 14 weeks. Each group consisted of six males and six females. Results: Females exhibited elevated LDL-cholesterol levels, while males presented higher creatinine levels and proteinuria. Enalapril effectively reduced blood pressure in both groups, but proteinuria decreased significantly only in females. Plaque size analysis and assessment of kidney inflammation revealed no significant sex-based differences. However, males displayed more severe glomerular injury, with increased mesangial expansion, mesangiolysis, glomerular foam cells and activated parietal epithelial cells (PECs). Enalapril mitigated mesangial expansion, glomerular inflammation (particularly in females), and the hypertrophy of PECs in males. Conclusion: This study demonstrates sex-based differences in the response to enalapril in a mouse model of atherosclerosis. Males exhibited more severe glomerular injury, while enalapril provided renal protection, particularly in females. These findings suggest potential sex-specific considerations for ACE inhibitor therapy in chronic kidney disease and atherosclerosis cardiovascular disease. Further research is needed to elucidate the underlying mechanism behind these observations.
ARTICLE | doi:10.20944/preprints202106.0733.v1
Subject: Engineering, Automotive Engineering Keywords: Discrete multiphysics; smooth particle hydrodynamics; Lattice Spring Model; Fluid-structure interaction; particle-based method; Coronary stent; Atherosclerosis
Online: 30 June 2021 (11:55:59 CEST)
Stenting is a common method for treating atherosclerosis. A metal or polymer stent is deployed to open the stenosed artery or vein. After the stent is deployed, the blood flow dynamics influence the mechanics by compressing and expanding the structure. If the stent does not respond properly to the resulting stress, vascular wall injury or re-stenosis can occur. In this work, Discrete Multiphysics is used to study the mechanical deformation of the coronary stent and its relationship with the blood flow dynamics. The major parameters responsible for deforming the stent are sort in terms of dimensionless numbers and a relationship between the elastic forces in the stent and pressure forces in the fluid is established. The blood flow and the stiffness of the stent material contribute significantly to the stent deformation and affect the rate of deformation. The stress distribution in the stent is not uniform with the higher stresses occurring at the nodes of the structure.
ARTICLE | doi:10.20944/preprints202308.0249.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: heart; ischemia; reperfusion; electrocardiography; ultra-high resolution electrocardiography; power spectral density; ischemic heart disease; subclinical atherosclerosis; sensitivity; risk stratification
Online: 3 August 2023 (05:17:42 CEST)
The sensitivity of exercise ECG is marginally sufficient for detection of mild reduction of coronary blood flow in patients with early coronary atherosclerosis. Here we describe the application of new technique of ECG registration/analysis – ultrahigh resolution ECG (UHR ECG) – for early detection of myocardial ischemia (MIS). The utility of UHR ECG vs. conventional ECG (C ECG) was tested in anesthetized rats and pigs. Transmural MIS was induced in rats by the ligation of the left coronary artery (CA). In pigs, subendocardial ischemia of variable extent was produced by stepwise inflation of balloon within the right CA causing 25-100% reduction of its lumen. In rats, a reduction in power spectral density (PSD) in high-frequency (HF) channel of UHR ECG was registered at 60 s after ischemia (power 0.81±0.14 vs. 1.25±0.12 mW at baseline, p<0.01). This was not accompanied by any ST segment elevation on C ECG. In pigs, PSD in HF channel of UHR ECG was significantly decreased at 25% reduction of CA lumen, while ST segment on C ECG remained unchanged. In conclusion, UHR ECG enabled earlier detection of transmural MIS compared to C ECG. PSD in HF-channel of UHR ECG demonstrated greater sensitivity in the settings of subendocardial ischemia.
REVIEW | doi:10.20944/preprints201809.0040.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Triggering receptor expressed on myeloid cells, DNAX-activating protein 12, cardiovascular diseases, atherosclerosis, coronary arteries diseases, acute myocardial infract, endocarditis
Online: 3 September 2018 (14:50:17 CEST)
Cardiovascular Diseases (CVDs) are still menacing and killing adults worldwide, notwithstanding the tremendous effort, to decrease their related mortality and morbidity. Lately, a growing body of evidences indicated that inflammation plays a pivotal role in the pathogenesis and complications of CVDs. A receptor of the immunoglobulin superfamily, triggering receptor expressed on myeloid cells -1 (TREM-1) was shown to induce and to amplify the inflammation in both acute and chronic diseases pathogenesis and progression and hence it is one of the important factors that complicates CVDs. Thus, studies endeavored to investigate the role played by TREM-1 in CVDs with respect to their etiologies, complications and possible therapeutics. We examined here, for the first time, the most relevant studies regarding TREM-1 involvement in CVDs. We summarized the finding after critically analyzing them and made some suggestions for furtherance of the investigations with the aim to utilize TREM-1 and its pathways for diagnostic, management and prognosis of CVDs. Overall, TREM-1 was found to be involved in the pathogenesis of acute and chronic cardiovascular conditions like Acute myocardial infraction (AMI) and atherosclerosis as well. Although most therapeutic approaches are yet to be elucidated, present research outcome displays a promising future to utilize TREM-1 pathway as potential target to understand and manage CVDs.
ARTICLE | doi:10.20944/preprints201809.0082.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: atherosclerosis; coronary aortic disease; gene set enrichment analysis; heart disease; Apoe mouse; transcriptomics; RNA-seq analysis; pathway enrichment analysis; mouse; precision medicine; New Zealand White rabbit
Online: 5 September 2018 (04:49:40 CEST)
The central promise of personalized medicine is individualized treatments that target molecular mechanisms underlying the physiological changes and symptoms arising from disease. We demonstrate a bioinformatics analysis pipeline as a proof-of-principle to test the feasibility and practicality of comparative transcriptomics to classify two of the most popular in vivo diet-induced models of coronary atherosclerosis, apolipoprotein E null mice and New Zealand White rabbits. Transcriptomics analyses indicate the two models extensively share dysregulated genes albeit with some unique pathways. For instance, while both models have alterations in the mitochondrion, the biochemical pathway analysis revealed, Complex IV in the electron transfer chain is higher in mice, whereas the rest of the electron transfer chain components are higher in the rabbits. Several fatty acids anabolic pathways are expressed higher in mice, whereas fatty acids and lipids degradation pathways are higher in rabbits. This reflects the differences between two translational models of atherosclerosis. This study validates transcriptome analysis as a potential method to precisely identify altered cellular and molecular pathways in atherosclerotic disease, which can be used to individualize treatment even in the absence of genetic data.
REVIEW | doi:10.20944/preprints202111.0253.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Cell therapy; chronic limb-threating ischemia; peripheral artery disease; diabetes; atherosclerosis obliterans; thromboangiitis obliterans; personalized medicine; artificial intelligence; machine learning; genome-wide association studies; transcriptome-wide association studies; clonal hematopoiesis of indeterminate potential.
Online: 15 November 2021 (11:18:43 CET)
Stem/progenitor cell transplantation is a potential novel therapeutic strategy to induce angiogenesis in ischemic tissue, which can prevent major amputation in patients with advanced peripheral artery disease (PAD). Thus, clinicians can use cell therapies worldwide to treat PAD. However, some cell therapy studies did not report beneficial outcomes. Clinical researchers suggested that classical risk factors and comorbidities may adversely affect the efficacy of cell therapy. Some studies have indicated that the response to stem cell therapy varies among patients even in those harboring limited risk factors. This suggested the role of undetermined risk factors, including genetic alterations, somatic mutations, and clonal hematopoiesis. Personalized stem cell-based therapy can be developed by analyzing individual risk factors. These approaches must consider several clinical biomarkers and perform studies (such as genome-wide association studies (GWAS)) on disease-related genetic traits and integrate the findings with those of transcriptome-wide association studies (TWAS) and whole-genome sequencing in PAD. Additional unbiased analyses with state-of-the-art computational methods, such as machine learning-based patient stratification, are suited for predictions in clinical investigations. The integration of these complex approaches into a unified analysis procedure for the identification of responders and non-responders before stem cell therapy, which can decrease treatment expenditure, is a major challenge to increase the efficacy of therapies.
REVIEW | doi:10.20944/preprints202203.0135.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: Aspirin; COVID-19; Human blood platelets; Platelet hemostatic function; Angiogenesis; Fatty acids; Immunity; Inflammation; Non-hemostatic function; Atherosclerosis; Cancer; Diabetes; Obesity; Hypertension; Bioactive compound; Water-soluble tomato extract; Kiwi fruit; Fruitflow®; papaya leaf extract; Polyphenols; Evodiamine; Polyphenols
Online: 10 March 2022 (02:42:26 CET)
Platelets have long been associated with sustaining the balance between hemostasis and thrombosis. Platelets, however, are also involved in a wide range of biological activities, including inflammation, immunology, wound healing, cancer biology, and angiogenesis. Platelets' diverse roles are mediated by the expression of various adhesive and immune receptors and the secretion of a diverse array of bioactive proteins, ions stored in granules, and several lipid mediators. Platelets also release pro-inflammatory and anti-inflammatory, and angiogenic factors and shed microparticles into the bloodstream. The challenge for therapeutic intervention in non-hemostatic disease is identifying the factors that primarily inhibit specific targets implicated in platelets' complicated contribution to inflammation or tumor growth while leaving their hemostatic function intact. In addition, blood platelets are involved in infection and innate and adaptive immunity by mediating complicated vascular homeostasis via specialized receptors and granule release, RNA transfer, and mitochondrial secretion. Anti-platelet drugs/bioactive compounds are developed based on their platelet anti-aggregatory properties; however, very little information is available on their effects on non-hemostatic function. Therefore, a better understanding of the impact of the anti-platelet bioactive on the platelets' diverse roles and mechanisms may help develop new strategies and prevent CVD and other diseases. In this review, a comprehensive overview of platelet multifunctional roles in CVD and other diseases and dietary factors' modulatory effects are described.