Background: The diagnosis of metabolic syndrome (MetS) is a challenge in people with spinal cord injury (SCI). We aimed at identifying clinical risk factors or early markers of MetS in SCI that would facilitate a timely diagnosis and implementation of preventive/therapeutic strategies. Methods: 168 patients with chronic (>1 year) SCI underwent clinical and biochemical evaluations. MetS was diagnosed according to modified criteria of the International Diabetes Federation validated in people with SCI. Results: MetS was diagnosed in 56 of 132 men (42.4%) and 17 of 36 women (47.2%). At univariate regression analyses, putative predictors of MetS were an older age, a higher number of comorbidities, a lower insulin-sensitivity, the presence and intensity of pain, a shorter injury duration, a poorer leisure time physical activity (LTPA) and an incomplete motor injury. At the multiple regression analysis, a significant independent association with MetS only persisted for a poorer LTPA in minutes/week (OR: 0.998, 95%CI: 0.996, 0.999) and more severe pain symptoms as assessed by numeral rating scale (OR: 1.353, 95%CI: 1.085, 1.793). Conclusions: In patients with SCI, intense pain symptoms and poor LTPA may suggest a high likelihood of MetS, regardless of age, SCI duration, motor disability degree, insu-lin-sensitivity and comorbidities.

Abstract Metabolic syndrome (MetS) is considered a metabolic disorder that has been steadily increasing globally and seems to parallel the increasing prevalence of obesity. It consists of a cluster of risk factors, which traditionally includes obesity and hyperlipidemia, hyperinsulinemia, hypertension, and hyperglycemia. These four core risk factors are associated with insulin resistance (IR) and importantly, the MetS is known to increase the risk for developing cerebrocardiovascular disease and type 2 diabetes mellitus. The MetS had its early origins in IR and syndrome X. It has undergone numerous name changes with additional risk factors and variables being added over the years; however, it still remains the MetS worldwide for the past three decades. This overview continues to add novel insights to the MetS and suggests that leptin resistance with hyperleptinemia, aberrant mitochondrial stress and reactive oxygen species (ROS), impaired folate-mediated one-carbon metabolism with hyperhomocysteinemia, vascular stiffening, microalbuminuria, and visceral adipose tissues extracellular vesicle exosomes be added to the list of associated variables. Notably, the role of a dysfunctional and activated endothelium and deficient nitric oxide bioavailability along with a dysfunctional and attenuated endothelial glycocalyx, vascular inflammation, systemic metainflammation, and the important role ROS and reactive species interactome are discussed. With new insights and knowledge regarding the MetS, comes the possibility of new findings through further research.

Endothelial integrity plays a major role in homeostasis and is responsive to the numerous endogenous factors released. While its functional role in vascular tone is well described, its role in the pathophysiology of cardiovascular disease is of interest as a potential therapeutic target. We performed a systematic review to provide an overview of new therapeutic and diagnostic targets for the treatment of coronary artery disease related to endothelial dysfunction. Databases of PubMed, Ovid’s version of MEDLINE, and EMBASE were interrogated with appropriate search terms. 28 studies met inclusion criteria and were included in the final systematic review. We identified inflammation, pulmonary hypertension, diabetes mellitus and Fabry disease as pathophysiological mechanisms and explored the therapeutic options related to these conditions including medications such as Canakinumab. Endothelial dysfunction has a key role in several different pathophysiological processes which can be targeted for therapeutic options. Ongoing research should be targeted at making the transition to clinical practice. Further research is also needed on understanding the amelioration of endothelial dysfunction with the use of cardiovascular medications.

Background: Brachial-ankle pulse wave velocity (baPWV) is widely used as a marker of arterial stiffness. It has been suggested as a simple method for detecting arterial loads that can trigger left ventricular hypertrophy in the heart. Increased left ventricular hypertrophy in hypertensive patients is a predictor that will have an impact on increasing morbidity and mortality. Objective: This study aimed to evaluate the correlation between the baPWV and the left ventricular mass index (LVMI) in hypertensive patients. Methods: This cross-sectional study was conducted by collecting secondary data from hypertensive patients at the Heart Outpatient Clinic, with inclusion: aged more than 40 years old, suffering hypertension more than one year, and had baPWV and echocardiography data. Correlation between baPWV and LVMI was evaluated using the Pearson correlation test. Results: A total of 40 hypertensive patients were enrolled in this study. 60% were women. The mean age was 52.92 ± 9.50 years. Mean LVMI was 107.20 + 21.01 gram/m2. LVMI showed a significant association with age and systolic blood pressure (p=0.001 and 0.019, respectively). Mean baPWV was 1832.90 + 336.22 cm/sec. A significant association was found between baPWV and age and systolic blood pressure (p=0.000 and 0.049, respectively). There was a significant positive correlation between baPWV and LVMI (r=0.493, p=0.001); and between baPWV and Relative Wall Thickness (RWT) (r=0.404, p=0.01). Conclusion: This study shows that elevated baPWV is an indicator of increased LVMI in hypertensive patients. Examination of baPWV should be carried out routinely to detect earlier arterial stiffness as a morbidity and mortality prevention strategy in hypertensive patients.

The prospective study enrolled 144 patients after surgical treatment of biliary atresia in early infancy. We analyze the immediate effectiveness of the surgery and the age-related structure of complications in the up to 16-year follow-up. The immediate 2-year survival rate after the surgery constituted 49.5%. At the time of this writing, 17 of the patients have celebrated their 10th birthdays with good quality of life and no indications for LT. The obtained results underscore the critical importance of surgical correction of BA by Kasai surgery during the first 60 days of life and subsequent dynamic follow-up of the patients for the purpose of the early detection and timely correction of possible complications.

Chronic conditions like type 2 diabetes mellitus (T2DM), arterial hypertension (HTN), and obesity are major global health issues, causing significant morbidity and mortality. In Latin America, these conditions contribute to millions of premature deaths annually, posing challenges exacerbated by limited healthcare access and poor primary care quality, particularly in Mexico. Complementary medicine presents a potential solution, offering minimally invasive techniques to improve physical, mental, and spiritual well-being. Effective treatment adherence, crucial for positive outcomes, is influenced by self-efficacy, the ability to manage one's behavior in response to medical conditions. However, treatment adherence rates remain low, indicating a pressing public health concern. This study aimed to explore how perception of complementary medicine and treatment adherence predict self-efficacy among individuals with chronic conditions in Mexico. Analyzing data from 113 participants revealed significant correlations between variables, with treatment adherence positively associated with self-efficacy and perception of holistic medicine negatively correlated with self-efficacy. Regression analysis showed that incorporating perception of complementary medicine and treatment adherence significantly explained self-efficacy levels, suggesting the potential of complementary therapies in holistic healthcare approaches. However, collinearity between variables highlights the need for further research to better understand these relationships and their implications for improving healthcare outcomes in Mexico. Integrating complementary therapies with conventional treatments could enhance overall well-being and treatment adherence, offering promising avenues for addressing chronic conditions in the region. These findings underscore the importance of comprehensive healthcare approaches that integrate both conventional and complementary modalities to optimize health outcomes and quality of life for individuals with chronic conditions in Mexico and beyond.

Gout is at least 3 times more prevalent in men than in women. However, concurrent with rising total gout prevalence, complex factors, including comorbidities, diet and lifestyle, and aging, have promoted higher gout prevalence in females. This narrative review focuses on summarizing recent developments in the landscape of gout in women, and mechanisms involved. New knowledge on sex hormone effects on both urate-excreting and urate-reabsorbing transporters, and higher hypertension and chronic kidney disease prevalence in women compared to men, may help explain why gout incidence rises robustly after menopause in women to approach that in men. Racial and ethnic factors, risk profiles based on heritable genetic polymorphisms of urate transporters, and diet, body mass index, and lifestyle factors differ according to sex. In addition, sex differences in clinical phenotypes and outcomes of gout and non-gout illnesses include more frequent comorbidities, more pain and disability during gout flare, different perceptions of disease burden, and more frequent severe cutaneous hypersensitivity reaction to allopurinol in women. Significantly, women with gout also have poorer COVID-19 outcomes than do men. Collectively, such findings support the potential clinical benefits of tailoring gout and hyperuricemia treatment according to sex.

Dysfunction and selective loss of retinal ganglion cells (RGCs) is a known cause of vision loss in glaucoma and other neuropathies where ocular hypertension (OHT) is the major risk factor. We investigated the impact of transient non-ischemic OHT spikes (spOHT) on RGC function and viability in vivo to identify cellular pathways linking low-grade repetitive mechanical stress to RGC pathology. We found that repetitive spOHT had an unexpectedly high impact on intraocular homeostasis and RGC viability, while exposure to steady OHT (stOHT) of similar intensity and duration failed to induce pathology. The repetitive spOHT induced a rapid activation of the inflammasome, marked by the upregulation of NLRP1, NLRP3, AIM2, caspases -1, -3/7, -8, gasdermin D (GsdmD) and the release of interleukin-1β (IL-1β) and other cytokines into the vitreous. Similar effects were also detected after 5 weeks of exposure to chronic OHT in an induced glaucoma model. The onset of these immune responses in both spOHT and glaucoma models preceded a 50% deficit in pattern electroretinograms (PERG) amplitude, and significant loss of RGCs at 7 days post-injury. Inactivation of inflammasome complexes in NLRP1-/- , Casp1-/- and GsdmD-/- knockout animals, significantly suppressed the spOHT induced inflammatory response and protected RGCs. Our results demonstrate that mechanical stress produced by acute repetitive spOHT or chronic OHT is mechanistically linked to inflammasome activation, which leads to RGC dysfunction and death.

Hypertension is one of the most common and significant cardiovascular risk factor. With the emergence of COVID-19, concerns have arisen about its potential to exacerbate cardiovascular morbidity and mortality. Several theories have emerged linking hypertension with COVID-19. However, the relationship between SARS-CoV-2 infection and long-term risk of hypertension remains insufficiently explored. Therefore, our study aimed to investigate the impact of COVID-19 infection on blood pressure and long-term risk of hypertension developing. A comprehensive search was conducted in the PubMed and SCOPUS databases up to 10th August 2023 for relevant papers. The analysis included 35 eligible articles. The majority of the latest studies pointed to increase BP after COVID-19 infection. However, several observations contradicted the influence of SARS-CoV-2 on the hypertension development or suggesting a transient effect. The possible role of the loss of angiotensin-converting enzyme 2, cytokine storm, increased sympathetic activity, and endothelial dysfunction were considered. On the other hand, BP changes following COVID-19 could be a consequence of lifestyle changes, which often accompanied COVID-19 infection. Our findings highlight the urgent need for comprehensive research on the COVID-19 and hypertension link. These insights are crucial for implementing effective prevention and management strategies for individuals with the history of COVID-19 infection.

Area covered: These drugs, particularly calcineurin inhibitors, have very narrow therapeutic windows, i.e., they have numerous drug-related side effects. Herein, we focus on the most frequent immunosuppressive drug-related side effects that we encounter in kidney-transplant recipients: namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). However, other therapies that are used after kidney transplantation, e.g., valcancyclovir, may also contribute to adverse events such as leukopenia. For each side-effect, we suggest how it can be prevented and how to treat it when present.

Pulmonary hypertension (PH) is a severe vascular complication of connective tissue diseases (CTD). Patients with CTD may develop PH belonging to different groups: 1) pulmonary arterial hypertension (PAH), 2) PH secondary to lung disease and/or hypoxia, 3) PH due to left heart disease, and 4) chronic thromboembolic pulmonary hypertension (CTEPH). PAH most often develops in systemic scleroderma (SSc), mostly in its limited variant. PAH-CTD is a progressive disease characterized by poor prognosis, therefore the early diagnosis should be established A specific treatment for PAH-CTD is currently available and recommended: prostacyclin derivative (treprostinil, epoprostenol, iloprost, selexipag), nitric oxide and natriuretic pathway: stimulators of soluble guanylate cyclase (sGC: riociguat) and phosphodiesterase 5 inhibitors (PDE5i: sildenafil, tadalafil), endothelin receptor antagonists (ERA: bosentan, macitentan, ambrisentan). Moreover, novel drugs e.g. sotatercept are intensively investigated in the clinical trials. The aim of this paper is to review the literature on the recent advances in treatment strategy and prognosis of patients with PAH-CTD.

Cardiac hypertrophy is an adaptive response to various pathological insults including hypertension. However, sustained hypertrophy can cause impaired calcium regulation, cardiac dysfunction, and remodeling, accompanied by cardiac fibrosis. Our previous study identified miR-25 as a regulator of SERCA2a, and that inhibition of miR-25 improved cardiac function and reduced fibrosis by restoring SERCA2a expression in a murine heart failure model. However, the precise mechanism underlying the reduction of fibrosis by miR-25 inhibition remains unclear. Therefore, we postulate that miR-25 may have additional targets that contribute to regulating cardiac fibrosis. Using in silico analysis, Krüppel-like factor 4 (KLF4) was identified as an additional target of miR-25. Further experiments confirmed that KLF4 was directly targeted by miR-25 and that its expression was reduced by long-term treatment with Angiotensin II, a major hypertrophic inducer. Subsequently, treatment with a miR-25 inhibitor alleviated the cardiac dysfunction, fibrosis, and inflammation induced by Angiotensin II. These findings indicate that inhibiting miR-25 not only enhances calcium cycling and cardiac function via SERCA2a restoration but also reduces fibrosis by restoring KLF4 expression. Therefore, targeting miR-25 may be a promising therapeutic strategy for treating hypertensive heart diseases.

A key feature of pulmonary arterial hypertension (PAH) is the hyperplastic proliferation exhibited by the vascular smooth muscle cells from patients (HPASMC). The growth inducers FOXM1 and PLK1 are highly upregulated in these cells. The mechanism by which these two proteins direct aberrant growth in these cells is not clear. Herein we identify cyclin dependent kinase 1 (CDK1) also termed cell division cycle protein 2 (CDC2), as having a primary role in promoting progress of the cell cycle leading to proliferation in HPASMC. HPASMC obtained from PAH patients and pulmonary arteries from Sugen/hypoxia rats were investigated for their expression of CDC2. Protein levels of CDC2 were much higher in PAH than in cells from normal donors. Knocking down FOXM1 or PLK1 protein expression with siRNA or pharmacological inhibitors lowered the cellular expression of CDC2 considerably. However, knockdown of CDC2 with siRNA or inhibiting its activity with RO-3306 did not reduce the protein expression of FOXM1 or PLK1. Expression of CDC2 and FOXM1 reached its maximum at G1/S, while PLK1 reached its maximum at G2/M phase of the cell cycle. The expression of other CDKs such as CDK2, CDK4, CDK6, CDK7 and CDK9 did not change in PAH HPASMC. Moreover, inhibition via Wee1 inhibitor adavosertib or siRNAs targeting Wee1, Myt1, CDC25A, CDC25B, or CDC25C led to dramatic decreases in CDC2 protein expression. Lastly, we found CDC2 expression at the RNA and protein level to be upregulated in pulmonary arteries during disease progression Sugen/hypoxia rats. In sum, our present results illustrate that the increased expression of FOXM1 and PLK1 in PAH leads directly to increased expression of CDC2 resulting in a potentiated growth hyperactivity of PASMC from patients with pulmonary hypertension. Our results further suggest that the regulation of CDC2, or associated regulatory proteins, will prove beneficial in the treatment of this disease.

Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of kidney damage in Renovascular hypertension (RVH). The activation of the Renin-Angiotensin System (RAS) is crucial in the development and progression of hypertensive renal damage and TGF-β is closely associated with the activation of RAS. In the present study, we assessed the effect of boldine on the progression of kidney disease using the 2K1C hypertension model and identifying mediators in the RAS such as TGF-β, that could be modulated by this alkaloid. Toward this hypothesis, rats (n=5/group) were treated with boldine (50mg/kg/day, gavage) for 6 weeks after 2K1C surgery (pressure≥180mmHg). Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive substances (TBARS). The evolution of systolic blood pressure (SBP) was followed weekly. α-SMA and Col III were used as markers of kidney damage; ED-1 and Osteopontin (OPN) as markers of inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF-β. Boldine treatment reduced UProt/UCrea ratio, plasma TBARS and slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED-1 and OPN were lower when compared to 2K1C rats. Boldine prevented the increase in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney damage. These results suggest that boldine could potentially be used as a nutraceutic.

Objective: The Rho GTPase/Rho kinase pathway is an important target in glaucoma treatment. This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor developed for cancer treatment, in a porcine ex vivo pigmentary glaucoma model. Materials and Methods: Twenty-eight fresh porcine anterior chambers were perfused with pigment medium (1.67 × 10⁷ pigment particles/mL) for 48 hours before being subjected to the RKI-1447 (n = 16) or the vehicle control (n = 12). Another twelve eyes with normal medium perfusion served as the control. The intraocular pressure (IOP) was recorded at two-minute intervals and the outflow facility was calculated. To investigate the intracellular mechanism of the IOP reduction, primary trabecular meshwork cells were exposed to RKI-1447 or the vehicle control and then analyzed for changes in cytoskeleton, motility, and phagocytosis. Results: Compared to the baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 mmHg to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 hours (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 exhibited no apparent changes in the micro- or macroscopic appearance, including histology. Primary TM cells exposed to RKI-1447 showed a significant disruption of the actin cytoskeleton both in the presence and absence of pigment exposure (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI reversed. Conclusions: RKI-1447 is a novel ROCK inhibitor that significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it especially useful for the treatment of secondary glaucomas with an increased phagocytosis load but also for other open angle glaucomas.

Heart failure is associated with a significant mortality rate, and an elevated prevalence of this condition has been noted among hypertensive patients. The identification of predictive factors for heart failure progression in hypertensive individuals is crucial for early intervention and improved patient outcomes. In this study, we aimed to identify these predictive factors utilizing medical history data for hypertension patients. Specifically, we focused solely on utilizing medical data preceding the diagnosis of hypertension to enable patients to anticipate the onset of potential heart failure at the time of hypertension diagnosis. Age-specific and ICD system-specific predictive factors were identified utilizing the MIMIC-IV database through the application of two analytical approaches: chi-square tests and XGBoost modeling. Our findings reveal 21 overall predictive factors, encompassing conditions such as atrial fibrillation, the use of anticoagulants, kidney failure, obstructive pulmonary disease, and anemia. These factors were assessed through a comprehensive review of the existing literature. We anticipate that the results will offer valuable insights for the risk assessment of heart failure in hypertensive patients.

World Health Organization recommends adjusting the salt intake as a part of the nine global targets to reduce premature mortality from non-communicable chronic diseases as priority and most cost-effective intervention. In 2006. the main aim of the Croatian Action on Salt and Health was to decrease salt intake for 16% because of its critical intake and consequences on human health. We have organized educative activities for increasing awareness on salt harmfulness, defined food categories of prime interest, collaborate with industries and determine salt intake (24h urine-sodium excretion). It was determined that the proportion of salt in ready-to-eat baked bread should not exceed 1.4%. In the period 2014 –2022, salt in the semi-white bread was reduced 14%, in bakery 22% and in largest meat industry in Croatia 25%. Awareness of the harmfulness of salt on health increased from 65.3% in 2008 to 96.9% in 2023 and salt intake was reduced 15.9%-1.8 grams/day (22.8% men, 11.7% women). In last 18 years a significant decrease in salt intake was achieved in Croatia, awareness of its harmfulness increased, collaboration with food industry established and regulatory documents launched. However, salt intake is still very high underlying the need for continuation of efforts and even stronger activities.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

The likelihood of pre-hypertensive young adults developing hypertension has been steadily increasing over the past few years. Despite the fact that aerobic exercise training (AET) has demonstrated positive results in lowering high blood pressure, the efficacy of different types of AET among pre-hypertensive young adults has not been well-established. The objective of this study was to evaluate the effectiveness of high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) on blood pressure (BP) of physically inactive pre-hypertensive young adults. 32 adults (age 20.0±1.1 years and BMI 21.5±1.8) were randomly assigned into 3 groups: HIIT, CMT and control (CON). HIIT and CMT groups participated in 5 weeks of AET; while the CON group followed a DASH diet plan only. The HIIT protocol consisted of 1:4 minute work to rest ratio of participants 80%-85% heart rate reserve (HR-reserve) and 40%-60% HR-reserve respectively for 20-minutes, CMT group exercised at 40%-60% of HR-reserve continuously for 20-minutes. In both HIIT and CMT groups, systolic blood pressure (SBP) (3.8±2.8 mmHg, P=0.002 VS 1.6±1.5 mmHg, P=0.011) was significantly reduced. While, significant reductions in the diastolic blood pressure (DBP) (2.9±2.2 mmHg, P=0.002) and mean arterial pressure (MAP) (3.1±1.6mmHg, P<0.0005) were noted only in the HIIT group. No significant differences in SBP (-0.4±3.7 mmHg, P=0.718), DBP (0.4±3.4 mmHg, P=0.714), or MAP (0.1±2.5mmHg, P= 0.892) were observed in the CON group. Both HIIT and CMT decreased the BP in physically inactive pre-hypertensive young adults; however, HIIT yielded more beneficial results in terms of reducing the SPB, DBP and MAP.

Circadian rhythms misalignment is associated with hypertension. The aim of the study was to evaluate the concentration of selected clock proteins- cryptochrome 1 (CRY1) and circadian locomotor output cycles kaput (CLOCK) and to determine their relationships with biochemical and anthropometric parameters and lifestyle elements (diet, physical activity, quality of sleep) in hypertensive patients. In 25 female with hypertension (HT) and 49 non-hypertensive women (NHT), the CRY1 and CLOCK concentrations, total antioxidant status (TAS), lipid profile and glycemia were conducted. Blood pressure and anthropometric measurements, nutritional, exercise and sleep analyses were performed. In HT the CRY1 level was 40.2% lower than in the NHT. No differences were noted in CLOCK concentration between groups. The study showed no relationship between CRY1 or CLOCK concentrations and glucose or lipids profile, amount of physical activity and sleep quality, although CRY1 was associated with some anthropometric parameters. There was a negative correlation between the CLOCK concentration and the amount of saturated fatty acids consumed (24h) in HT. That indicates the possible influence of the diet on the CLOCK level. In a detailed prognosis of the risk of hypertension, it is worth considering the measurement of the level of CRY1 in populations with abnormal anthropometric indices.

The normal ageing process significantly affects resistance arteries, leading to various biological and physiological consequences. Systolic hypertension is a common occurrence in ageing individuals, accompanied by increased large artery stiffening, heightened pulsatility, small artery remodeling, and damage to critical microvascular structures. Starting from young adulthood, there is a progressive elevation in mean arterial pressure, supported by clinical and epidemiological evidence as well as findings from animal models. The myogenic response, a protective mechanism for the microcirculation, may face disruptions during ageing. Dysregulation of calcium entry channels (T-type, L-type, TRP channels), dysfunction in intracellular calcium storage and extrusion mechanisms, altered expression of potassium channels, and a change in smooth muscle calcium sensitization may contribute to age-related dysregulation of myogenic tone. Flow-mediated vasodilatation, a hallmark of endothelial function, is compromised in ageing. This result of endothelial dysfunction is related to oxidative stress, lower nitric oxide bioavailability and a low-grade inflammatory response, further exacerbating vascular dysfunction. Resistance artery remodeling in ageing emerges as a hypertrophic response of the vessel wall, often seen in conjunction with outward remodeling (in normotension), but can also present as inward hypertrophic remodeling (in hypertension). The remodeling process involves oxidative stress, inflammation, reorganization of extracellular matrix fiber proteins and actin cytoskeletal components. Reactive oxygen species (ROS) signaling and chronic low-grade inflammation, often referred to as "inflammaging”, play substantial roles in age-related vascular dysfunction. Due to its role in regulation of vascular tone as well as structural proteins, the RhoA/Rho-kinase pathway becomes a new target in age-related vascular dysfunction and associated diseases. Understanding the intricate interplay of these factors is crucial for developing targeted interventions to mitigate the consequences of ageing on resistance arteries and enhance overall vascular health.

The aim of the present study was to investigate whether chronic undernutrition modifies the response to rostafuroxin in juvenile rats. Chronic undernutrition was induced in male rats using a multideficient diet known as Regional Basic Diet (RBD), mimicking alimentary habits in impoverished regions worldwide. Animals were given RBD – or a control/CTRL normal diet for rodents – from weaning to 90 days, and rostafuroxin (1 mg/kg body mass) or vehicle were orally administered during the last 30 days. Undernourished rats became hypertensive at 55–60 days of age (tail-cuff recording). During the last two days, the rats were hosted in metabolic cages to measure food/energy, water, Na⁺ ingestion, and urinary volume. Blood and kidneys were collected after euthanasia. Rostafuroxin increased food/energy and Na⁺ intake in CTRL and RBD rats but had opposite effects on Na⁺ balance (intake minus urinary excretion): negative in CTRL and positive in RBD. The drug normalized the decreased plasma Na⁺ concentration found in RBD rats, increased urinary volume in RBD but not in CTRL, and decreased and increased urinary Na⁺ concentration in the RBD and CTRL groups, respectively. Rostafuroxin decreased the ouabain-sensitive (Na⁺+K⁺)ATPase and increased the ouabain-resistant, furosemide-sensitive Na⁺-ATPase from proximal tubule cells in both groups, and normalized the systolic blood pressure in RBD without effect in CTRL rats. We conclude that chronic undernutrition modifies the response of blood pressure, caloric metabolism, Na⁺ distribution in liquid compartments, mobilization of Na⁺ from non-osmotic compartments, Na⁺ and water balance, and activity of renal Na⁺-transporting ATPases to rostafuroxin.

The aim of the present study was to investigate whether chronic undernutrition modifies the response to rostafuroxin in juvenile rats. Chronic undernutrition was induced in male rats using a multideficient diet known as Regional Basic Diet (RBD), mimicking alimentary habits in impoverished regions worldwide. Animals were given RBD – or a control/CTRL normal diet for rodents – from weaning to 90 days, and rostafuroxin (1 mg/kg body mass) or vehicle were orally administered during the last 30 days. Undernourished rats became hypertensive at 55–60 days of age (tail-cuff recording). During the last two days, the rats were hosted in metabolic cages to measure food/energy, water, Na+ ingestion, and urinary volume. Blood and kidneys were collected after euthanasia. Rostafuroxin increased food/energy and Na+ intake in CTRL and RBD rats but had opposite effects on Na+ balance (intake minus urinary excretion): negative in CTRL and positive in RBD. The drug normalized the decreased plasma Na+ concentration found in RBD rats, increased urinary volume in RBD but not in CTRL, and decreased and increased urinary Na+ concentration in the RBD and CTRL groups, respectively. Rostafuroxin decreased the ouabain-sensitive (Na++K+)ATPase and increased the ouabain-resistant, furosemide-sensitive Na+-ATPase from proximal tubule cells in both groups, and normalized the systolic blood pressure in RBD without effect in CTRL rats. We conclude that chronic undernutrition modifies the response of blood pressure, caloric metabolism, Na+ distribution in liquid compartments, mobilization of Na+ from non-osmotic compartments, Na+ and water balance, and activity of renal Na+-transporting ATPases to rostafuroxin.

COVID-19 affects many organs in our body, including the heart and lungs. COVID-19 cases that require hospitalization often exhibit pulmonary hypertension (PH) due to changes in the lung microvasculature in which the blood vessels become stiff, damaged, or narrow, causing increased pulmonary arterial pressure. This review examines the hypothesis that PH can lead to right ventricular hypertrophy (RVH) as a long-lasting aftereffect of COVID-19. Recent studies have shown that significant percentages of hospitalized patients develop right ventricular hypertension and right ventricular dilatation (RVD), which may lead to right ventricular failure and death. Despite recommendations for echocardiogram reports to include right ventricular wall thickness to assess RVH, few published reports have reported this parameter. Relevant studies on animal models of PH in which the timing of PH can be precisely controlled suggest that one to three weeks of PH can cause RVH. Thus, according to the hypothesis proposed here COVID-19 patients who have long-lasting severe disease (e.g., needed to be on a ventilator for one or more weeks) accompanied by PH and RVD may develop RVH as a long-lasting sequela outlasting the infection itself. Echocardiogram studies of recovered COVID-19 patients may determine whether oft-reported cardiovascular sequelae include RVH.

Overweight/obesity is a growing pandemic nowadays that affects many organs and tissues. We have investigated whether a high-lipid diet provokes an imbalance between type 1 and type 2 angiotensin II (Ang II) receptors signaling, leading to liver alterations associated with previously described cardiovascular and kidney disturbances. Chronic administration of a high-lipid diet can provoke an hepatocardiorenal syndrome as the result of activation of the Ang II→type 1 receptor axis, which is completely counteracted by Ang-(3–4) the allosteric enhancer of the Ang II→type 2 receptor pathway.

There are evidences of shared biological mechanisms between obesity and hypertension during childhood in the adulthood, and loads of research literatures have proven that, it will cost the economies and health of nations profoundly if neglected. The Prevention and early diagnosis of cardiovascular risk factors such as overweight and hypertension is an essential strategy for control, effective treatment and prevention of its’ complications. The aim of the study is to assess the effect of school based Exercise and Life style Motivation Intervention (SEAL-MI) on adolescent's cardiovascular risk factors and academic performance. An experimental study was conducted among 1005 adolescents - 520 and 485 adolescents were randomly selected for control and study group, respectively. Demographic details and the data related to dietary habits, physical activity and sleep quality were collected by a structured interview questionnaire. The study group adolescents were given the SEAL-MI for six months which includes a school based rope exercise for 45 minutes per day for 5 days a week and a motivation intervention related to dietary habits, physical activity and sleep. Post-test 1 and 2 were done after 3 and 6 months of intervention. The prevalence of overweight among adolescents was 28.73% and prehypertension was 9.26%. Among overweight adolescents, the prevalence of prehypertension was found to be very high (32.25%). In post intervention, there was a significant reduction in weight, BP (p=0.000) and improvement in dietary habits, physical activity, sleep (p=0.000) and academic performance. A significant positive correlation was found between BMI and SBP (p=0.000) and BMI and academic performance (p=0.003). The linear regression analyses revealed that the gender (ß: 0.47, 95% CI: 0.39, 0.81), age (ß: 0.39, 95% CI: 0.17, 0.46), family income (ß: 0.2, 95% CI: 0.41, 0.5), residence (ß: 0.19, 95% CI: 0.01, 0.27) and type of family (ß: 0.25, 95% CI: 0.39, 0.02) had the strongest correlate with the BMI of the adolescents. Also, Mother’s education Mother’s education (ß: 0.35, 95% CI: 0.18, 0.59) had the strongest correlate with the SBP of the adolescents. In contrast, the DBP was negatively persuaded by age (ß: -0.36, 95% CI: 1.54, 0.29) and gender (ß: -0.26, 95% CI: 1.34, 0.12) of the adolescents. Regular practice of rope exercise and lifestyle modification such as diet, physical activity and sleep quality among adolescents prevent and control childhood CVD risk factors like overweight, hypertension. The SEAL-MI may lead to age appropriate development of adolescents and improves their academic performance and quality of life. Giving importance to the adolescents from urban habitat, from affluent nuclear family and catching them young will bring significant change in the disease burden.

Abstract: The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRa and GRb), has been implicated in the development of primary open-angle glaucoma (POAG) and iatrogenic glucocorticoid-induced glaucoma (GIG). POAG is the most common form of glaucoma, which is the leading cause of irreversible vision loss and blindness in the world. Glucocorticoids (GCs) are commonly used therapeutically for ocular and numerous other diseases/conditions. One serious side effect of prolonged GC therapy is the development of iatrogenic secondary ocular hypertension (OHT) and OAG (i.e. GC-induced glaucoma (GIG)) that clinically and pathologically mimics POAG. GC-induced OHT is caused by pathogenic damage to the trabecular meshwork (TM), a tissue involved in regulating aqueous humor outflow and intraocular pressure. TM cells derived from POAG eyes (GTM cells) have lower expression of GRb, a dominant negative regulator of GC activity, compared to TM cells from age-matched control eyes. Therefore, GTM cells have a greater pathogenic response to GCs. Almost all POAG patients develop GC-OHT when treated with GCs, in contrast to a GC responder rate of 40% in the normal population. Increased expression of GRb can block GC-induced pathogenic changes in TM cells and reverse GC-OHT in mice. Endogenous expression of GRb in the TM may relate to differences in the development of GC-OHT among the normal population. A number of studies have suggested increased levels of endogenous cortisol in POAG patients as well as differences in cortisol metabolism, suggesting that GCs may be involved in the development of POAG. Additional studies are warranted to better understand the molecular mechanisms involved in POAG and GIG in order to develop new disease modifying therapies to better treat these two sight threatening forms of glaucoma.

Individuals diagnosed with systemic arterial hypertension (SAH) are considered risk groups for COVID-19 severity. This study assessed differences in cardiac autonomic function (CAF) and functional capacity (CF) in SAH individuals without COVID-19 infection compared to SAH individuals post-COVID-19. Participants comprised 40 SAH individuals aged 31 to 80 years old, grouped as SAH with COVID-19 (G1; n=21) and SAH without COVID-19 (G2; n=19). CAF was assessed via heart rate variability (HRV), measuring R-R intervals during a 10-minute supine period. Four HRV indices were analyzed through symbolic analysis: 0V%, 1V%, 2LV%, and 2UV%. FC assessment was performed by a 6-minute walk test (6MWT). G1 and G2 showed no difference between significant age, anthropometric, clinical and medication. G2 exhibited superior 6MWT performance, covering more distance (522±78 vs. 465±59 meters, p&lt;0.05). Specifically, G2 demonstrated a moderate, positive correlation between 6MWT and the 2LV% index (r=0.58; p&lt;0.05). Shorter walking distances were observed during 6MWT in SAH individuals post-COVID-19. However, the study did not find impaired cardiac autonomic function in SAH individuals post-COVID-19 compared to those without. This suggests that while COVID-19 impacted FC, CAF remained relatively stable in this population.

Cardiopulmonary complications remain the major cause of mortality despite newer therapies and improvements in lifespan of patients with sickle cell disease (SCD). Inflammation has been identified as a major risk modifier in the pathogenesis of SCD associated cardiopulmonary complications in recent mechanistic and observational studies. In this review, we discuss recent cellular and molecular mechanisms of cardiopulmonary complications in SCD and summarize the most recent evidence from clinical and laboratory studies. We emphasize the role of inflammation in the onset and progression of these complications to better understand the underlying pathobiological processes. We also discuss future basic and translational research in addressing questions about the complex role of inflammation in the development of SCD cardiopulmonary complications, which may lead to promising therapies and reduce morbidity and mortality in this vulnerable population.

This review focuses on the emerging evidence for the association between estimated cardiorespiratory fitness (eCRF) and metabolic risk factors. Given the challenges associated with directly measuring cardiorespiratory fitness (CRF) in large populations, eCRF presents a practical alternative for predicting metabolic health risks. A literature search identified six relevant cohort studies from 2021 to 2024 that investigated the association of eCRF with hypertension, hyperglycemia, dyslipidemia, and obesity. The review findings highlight a consistent inverse relationship between higher eCRF and lower incidence of metabolic risks in line with CRF cohort studies. This review highlights the importance of low eCRF as a primordial indicator for metabolic risks and underscores the need for broader application. Future research directions should include exploring eCRF's predictive accuracy across diverse populations and health outcomes and testing its real-world applicability in healthcare and public health settings.

A growing number of clinical data suggests that the use of antiplatelets and/or statins pre-stroke are associated with reduced severity and better functional outcomes for ischemic stroke. Studies have shown that the long-term use of ACEI/ARB pre-stroke is beneficial in reducing severity at onset and improving functional outcomes. We aimed to compare stroke severity and early functional outcome between patients taking ACEI/ARB and those who were not, and to identify any additional effects to taking ACEI/ARB with antiplatelets, statins, or both. In this retrospective case-control study, we assessed 218 patients who presented with ischemic stroke to the stroke unit in Padeh-Poriyah Hospital between 2019-2020. Of these patients, 119 took ACEI/ARB pre-stroke. A significantly higher percentage of ACEI/ARB-treated patients had a history of hypertension (HTN) and hyperlipidemia and were taking antiplatelets and/or statins, compared to the non-ACEI/ARB group. We observed that pre-stroke treatment with ACEI/ARB is associated with worsened stroke severity and reduced early functional outcomes. No significant benefit to taking ACEI/ARB with antiplatelets and/or statins pre-stroke was observed. Due to the nature of our study, the data should be interpreted as suggestive. Thus, prospective studies of these medications on ischemic stroke severity and early outcomes are warranted.

A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.

This cross-sectional study evaluated the validity of three alternative methods compared to the gold standard 24-h urine collection for estimating dietary sodium intake, a modifiable risk factor for hypertension, among middle-aged and older adults with elevated blood pressure. These included spot urine collection (using Kawasaki, Tanaka, and INTERSALT equations), 24-h dietary recall, and food frequency questionnaire responses, compared against 24-h urine collection in a subset of 65 participants (aged 50–75 years, 58.5 % women, 61.6 % hypertensive) from the DePEC-Nutrition trial. The validity of the methods was assessed using bias, Spearman correlation coefficient (SCC), intraclass correlation coefficient (ICC), and Bland-Altman analysis. Among the alternative methods, spot urine collection using the Kawasaki equation showed the strongest correlation (SCC 0.238; ICC 0.119, 95 % CI -0.079 to 0.323) but it exhibited a significant bias (1414 mg/day, p-value < 0.001) relative to 24-h urine collection. Conversely, dietary surveys had a smaller bias but wider limits of agreement. These findings underscore the complexities of accurately estimating dietary sodium intake using spot urine collection or dietary surveys in this specific population, suggesting that a combination or refinement of existing methodologies might improve accuracy. Further research with larger samples is necessary to develop more reliable methods for assessing sodium intake in this high-risk group.

In New Orleans, Louisiana the population’s poor baseline health led to its establishment as an early epicenter for severe acute COVID-19. Antici-pating future outbreaks of COVID-19 and other respiratory viruses, we need to identify correlates of outcome, from real clinical experience. 89 patients were recruited into the ClinSeqSer acute COVID-19 longitudinal observational study, from the beginning of the outbreak in March to July 2020. Patients admitted for acute COVID-19 were enrolled in person. The cohort is unique as it is 68% Black, 53% female, of average age of early 60s, and prevalence of obesity and hypertension respectively of 55% and 83%. The outcomes are: 53% severe (20% fatal, 33% non-fatal) and 47% non-severe, with severe defined as death or requiring mechanical ventila-tion or high flow oxygen. Obesity and admit systolic blood pressure (SBP) >140mmHg are each associated with severe outcome and, despite respective sensitivity of 71% and 76%, specificity ~66% for both, and ac-curacy of 60% and 70% by ROC analysis, would likely provide useful predictors of outcome in critically stressed health care systems. We discuss pathophysiologic hypotheses to explain why high admit SBP is observed only in half of patients with pre-COVID hypertension and is associated with severe outcome.

Background: The annual mortality of patients with untreated chronic thromboembolism pulmonary hypertension (CTEPH) is approximately 50% unless a timely diagnosis is followed by adequate treatment. In pulmonary embolism (PE) survivors with functional limitation the diagnostic work-up starts with echocardiography. It is followed by lung scintigraphy and right heart catheterization. However, noninvasive test providing diagnostic clues to CTEPH, or ascertain this diagnosis as very unlikely, would be extremely useful since the majority of post PE functional limitations is caused by deconditioning. Methods: Patients after acute PE underwent a structured clinical evaluation with electrocardiogram, routine laboratory tests including NT-proBNP and echocardiography. The aim of study was to verify whether the parameters from echocardiographic or perhaps electrocardiographic examination and NT-proBNP concentration best determine the risk of CTEPH. Results: A total (n = 261, male n = 123) patients after PE were included into the study, in group of 155 patients (59.4%) with reported functional impairment 13 patients (8.4%) had CTEPH and 7 PE survivors had chronic thromboembolic pulmonary disease (CTEPD) (4,5%). Echo parameters differed significantly between CTEPH/CTEPD cases and other symptomatic PE survivors. Patients with CTEPH/CTEPD had also higher level of NT-proBNP (p = 0.022) but concentration of NT-proBNP above 125 pg/ml did not differentiate patients with CTEPH/CTEPD (p>0.05). Additionally, proportion of patients with right bundle brunch block registered in ECG was higher in group with CTEPH/CTED (23.5% vs. 5.8%, p = 0.034) but there were no differences between other ECG characteristics of right ventricle overload. Conclusion: Screening for CTEPH/CTEPD should be performed in patients with reduced exercise tolerance compared to pre PE period, It is not effective in asymptomatic PE survivors. Patients with CTEPH/CTED had predominantly abnormalities indicatingchronic thromboembolism in the echocardiographic assessment. NT-proBNP and electrocardiographic characteristics of right ventricle overload proved to be insufficient in predicting CTEPH/CTEPD development.

We aimed to delineate cardiopulmonary interactions in acute bronchiolitis and to evaluate the capacity of a combined cardiopulmonary ultrasonography to predict the need for respiratory support. This was a prospective observational single-center study that includes infants < 12 month of age admitted to a hospital due to acute bronchiolitis. All the included patients under-went clinical, laboratory and cardiopulmonary ultrasonographic evaluation at the same time point within 24 hours of hospital admission. The existence of significant correlation between car-diac and respiratory parameters was the primary outcome. The association of different cardio-pulmonary variables with the need of respiratory support higher than O2, the length of stay hos-pitalization, the PICU stay, and the duration of respiratory support were a secondary outcome. We enrolled 112 infants (median age 1 (0.5-3) months; 62% males) hospitalized with acute bron-chiolitis. Increased values of the pulmonary variables (BROSJOD score, pCO2 and LUS) showed moderate correlations with NT-proBNP and all echocardiographic parameters indicative of pulmonary hypertension and myocardial dysfunction. Up to 36 (32%) infants required respira-tory support during the hospitalization. This group presented with higher lung ultrasound score (p<0.001), and increased values of Tei index (p<0.001) and pulmonary artery pressures (p<0.001). All the analyzed respiratory and cardiac variables showed moderate to strong correlations with the LOS hospitalization and the time of respiratory support. Lung ultrasound and echocardiog-raphy showed a moderate to strong predictive accuracy for the need of respiratory support in the ROC analysis, with AUC varying from 0.74 to 0.87. Conclusion: Those cases of bronchiolitis with a worse pulmonary status presented with a more impaired cardiac status. Cardiopulmonary ul-trasonography could be a good strategy to easily identify high-risk population for a complicated acute bronchiolitis hospitalization.

(1) Background: Co-morbidities such as hypertension and cardiovascular disease are major risk factors for severe COVID-19. The renin-angiotensin-system (RAS) is critically involved in their pathophysiology and is counterbalanced by both angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and the kallikrein-kinin-system (KKS). Considerable research interest with respect to COVID-19 treatment is, thus, currently directed towards the components of these systems. In an earlier study, we noticed significantly reduced carboxypeptidase N (CPN, KKS member) activity and partially excessive angiotensin-converting enzyme (ACE, RAS member) activity in the sera of both hospitalized (HoP) COVID-19 patients and a sub-group of covalescent patients, while in the majority of the probands recovering from the disease these values had returned to normal. The data had been obtained using bradykinin (BK) as a reporter peptide, which is a target of both CPN and ACE, and they were supplemented by serum proteomics of the same patient cohort. We hypothesized that the data could be indicative of Long COVID, which had not been fully appreciated at the time of our study.; (2) Methods: The data were re-evaluated in the light of Long COVID. The recent literature on the RAS in COVID-19, antihypertensiva, and Long COVID was briefly reviewed.; (3) Results: While the levels of the BK serum degradation products should return to normal concentrations during convalescence, this was not true for some patients. This could be due to persisting liver problems, because CPN is synthesized there, but also to a dysregulated RAS. This was not reflected in the levels of selected RAS/KKS serum proteins like angiotensinogen (AGT), although AGT correlated with disease severity in HoP. However, standard tests in routine patient care in Long COVID often come back normal, and it may be that BK degradation is specific in some pathophysiologies. Moreover, the HoP group was sub-divided based on the serum protein profiles and COVID-19 severity.; (4) Conclusions: We point out two insights: 1) Sensitive technology such as omics methods might provide unexpected significant differences within the pre-defined patient groups of a clinical study. Those can only be explored, if the cohorts are large enough and properly matched with respect to the parameters known beforehand (e.g., age, gender, co-morbidities). 2) Results of the BK-reporter serum protease activity assay could be indicative of persisting liver problems and/or potentially of Long COVID. Clinical studies are required to test this hypothesis.

The pressure exerted on the heart and blood vessels because of blood flow is considered as an important parameter for the cardiovascular function. It determines sufficient blood perfusion as well as transportation of nutrition, oxygen and other essential factors to every organ. Pressure in the primary arteries located near the heart and the brain, known as central blood pressure (CBP), while in peripheral arteries, known as peripheral blood pressure (PBP). Normally, CBP and PBP are correlated; however, cardiovascular disorders interfere their regulation and affect the blood flow in vital organs and accessory organs, differently. Therefore, understanding each of them in normal and disease conditions is essential for managing various cardiovascular disorders and increasing their treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic and cellular) of the blood pressure and its regulation in hypovolemic shock using centhaquine (Lyfaquin®) as a resuscitative agent.

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing in-creased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play im-portant roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB de-pendence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter en-dothelial function or the contractile response to phenylephrine in these arteries. In contrast, CIH exposure increased the systemic arterial pressure, and enhanced the contractile response to phenylephrine while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta, without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

Background Although high-density lipoprotein has cardioprotective effects, the association between serum high-density lipoprotein cholesterol (HDL-C) and hypertension is poorly understood. Objective We investigated whether low and high concentrations of HDL-C are associated with hypertension using a large healthcare dataset. Methods In a community-based cross-sectional study of 1,493,152 Japanese people aged 40–74 years who underwent a health checkup, blood pressures and clinical parameters, including nine HDL-C concentrations (20–110 mg/dL or over) were investigated. Results A crude U-shaped relationship was observed between the nine HDL-C concentrations and blood pressure in males (n = 830,669), while a left-to-right inverted J-shaped relationship was observed in females(n = 662,483). An age-adjusted logistic regression analysis showed J-shaped relationships (left-to-right inversion in females) between HDL-C and odds ratios for hypertension (≥140/90 mmHg), with lower limits of 60–79 mg/dL in males and 90–99 mg/dL in females, which were unchanged after adjusting for smoking, habitual exercise, alcohol consumption, and pharmacotherapy for hypertension, dyslipidemia, and diabetes. However, further adjustment for body mass index and serum triglyceride concentration revealed latent positive linear associations between HDL-C and hypertension, although the association between extremely high HDL-C (≥100 mg/dL) and hypertension was attenuated in non-alcohol drinkers. Conclusion Both low and extremely high HDL-C concentrations are associated with hypertension. The former association may be dependent on excess fat mass, which is often concomitant with low HDL-C, whereas the latter association may be dependent on frequent alcohol consumption.

Background. Epidemiological and clinical studies demonstrated that excessive salt intake causes severe hypertension and exacerbated organ derangement such as chronic kidney disease (CKD). In this study, we focused on evaluating histological and gene-expression findings in the kidney using stroke-prone spontaneously hypertensive rats (SHRSP) with high-salt intake and thromboxane A2/ prostaglandin H2 receptor (TPR) blocker ONO-8809. Methods. SHRSP aged 6 weeks were divided into three groups eating normal chow containing 0.4% NaCl, 2.0%NaCl, or 2.0%NaCl +ONO-8809 (0.6mg/kg p.o. daily). Histological analyses with immunohistochemistry and a gene-expression assay with a DNA kidney microarray were performed after 8 weeks. Results. The following changes were observed with high-salt intake. Glomerular sclerotic changes were remarkably observed in the juxtaglomerular cortex areas. ED1, MCP-1, nitrotyrosine, and HIF-1α staining areas were increased in the glomeruli and interstitial portion. Tbxa2r which encodes TPR, Prcp, and Car7 were significantly underexpressed in the kidney. The plasma 8-isoprostane level was significantly elevated, and was attenuated with ONO-8809 treatment. Conclusion. TXA2 and oxidative stresses exaggerated renal dysfunction in salt-loading SHRSP, and ONO-8809 as a TPR blocker suppressed these changes. Therefore, ONO-8809 is a candidate drug to prevent CKD for hypertensive patients associated with high-salt intake.

Acute high altitude illnesses are of great concern for physicians and people traveling to high altitude. High Altitude Pulmonary Edema (HAPE) can be better understood through the Oxygen Transport Triad which involves the Pneumo-Dynamic Pump (Ventilation), the Hemo-Dynamic Pump (Heart and circulation), and Hemoglobin. The two pumps are the first physiologic response upon initial exposure to hypobaric hypoxia. Hemoglobin is the balancing energy-saving time-evolving equilibrating factor. The increased hemoglobin at high altitude reduces the percentage of dissolved oxygen in the arterial oxygen content with respect to sea level. At high altitude, the acid-base balance must be adequately interpreted using the high altitude Van-Slyke correction factors. Pulse-oximetry measurements during breath-holding at high altitude allow for the evaluation of high altitude diseases. The Tolerance to Hypoxia Formula shows that, paradoxically, the higher the altitude the more tolerance to hypoxia. All organisms adapt physiologically and optimally to a high-altitude environment to survive. Reduction of pulmonary hypertension in HAPE through oxygen administration results in a favorable outcome.

Posttraumatic stress disorder (PTSD) and/or specific PTSD symptoms may evoke disordered eating and unhealthy lifestyles, resulting in adverse cardiometabolic events (e.g., hypertension and obesity) in certain groups, which may implicate the treatment of this complex condition. The diagnostic criteria of PTSD have lately expanded beyond the three common symptoms (intrusion, avoidance, and hyperarousal). Simultaneously, four-, five-, and six-dimensional structures of the Impact of Event Scale-Revised (IES-R), a popular PTSD measure, seem to be more robust than the original three-dimension structure. Within the context of COVID-19, this instrumental study used a convenience sample of 58 dental healthcare workers (HCWs) from Russia (mean age = 44.1±12.2 years, 82.8% females) to examine the criterion and predictive validity of two IES-R structures: the IES-R3 and the IES-R6 (with the added symptoms of numbing, sleep disturbance, and irritability). The subscales of the two IES-R structures expressed good internal consistency, strong correlations with the PTSD Symptom Scale (PSS), hypertension diagnosis, and high body mass index (BMI). In receiver-operating characteristic (ROC) curve analysis, all IES-R models perfectly predicted the PSS (all area under the curve (AUC) >0.9, p values <0.001). The IES-R, both hyperarousal subscales, and the IES-R3 intrusion subscale significantly predicted high BMI. Both avoidance subscales and the IES-R3 intrusion subscale, not the IES-R, significantly predicted hypertension. In conclusion, both IES-R structures can reliably measure PTSD symptoms. The IES-R, hyperarousal, and intrusion may be credible criterion variables for predicting high BMI within PTSD while the intrusion and avoidance subscales may reflect the cardiovascular consequences associated with PTSD more reliably than the IES-R itself. The IES-R subscales may predict cardiometabolic adversities in PTSD, signifying a need for proper assessment of lifestyle and the application of dietary and exercise interventions in order to lower physical morbidity in PTSD. Replicating the study in larger samples, which comprise different physical and mental conditions from heterogenous cultural contexts is pivotal to validate the results (e.g., in specific groups such as those with confirmed traumatic exposure and comorbid mood dysfunction).

Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

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.