REVIEW | doi:10.20944/preprints202105.0735.v1
Subject: Medicine & Pharmacology, Allergology 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
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 & Pharmacology, Cardiology 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 & Pharmacology, Cardiology 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.
REVIEW | doi:10.20944/preprints202009.0301.v1
Subject: Life Sciences, Immunology 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 & Pharmacology, Cardiology 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.
ARTICLE | doi:10.20944/preprints202104.0154.v1
Subject: Medicine & Pharmacology, Allergology 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 & Pharmacology, Cardiology 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/preprints202008.0083.v1
Subject: Medicine & Pharmacology, Cardiology 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.
ARTICLE | doi:10.20944/preprints202102.0577.v1
Subject: Medicine & Pharmacology, Allergology 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: Medicine & Pharmacology, Nutrition 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, Animal Sciences & 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 & Pharmacology, Clinical 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 & Pharmacology, Pharmacology & 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, Other 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.
REVIEW | doi:10.20944/preprints201806.0239.v1
Subject: Medicine & Pharmacology, General Medical Research 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: Life Sciences, Other 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/preprints202008.0457.v1
Subject: Life Sciences, Biochemistry 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
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/preprints202201.0241.v1
Subject: Medicine & Pharmacology, Clinical 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 & Pharmacology, Other 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 & Pharmacology, Cardiology 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 & Pharmacology, Cardiology 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, Other 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 & Pharmacology, Cardiology 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.
ARTICLE | doi:10.20944/preprints202112.0073.v1
Subject: Life Sciences, Endocrinology & Metabolomics 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 & Pharmacology, Cardiology 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 & Pharmacology, Cardiology 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/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.
REVIEW | doi:10.20944/preprints201809.0040.v1
Subject: Medicine & Pharmacology, Cardiology 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 & Pharmacology, Cardiology 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 & Pharmacology, Cardiology 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: Medicine & Pharmacology, Nutrition 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.