Aspects Of Cardiovascular Disease Research Articles

Management of Cardiovascular Diseases by Short-Chain Fatty Acid Postbiotics.

Global health concerns persist in the realm of cardiovascular diseases (CVDs), necessitating innovative strategies for both prevention and treatment. This narrative review aims to explore the potential of short-chain fatty acids (SCFAs)-namely, acetate, propionate, and butyrate-as agents in the realm of postbiotics for the management of CVDs. We commence our discussion by elucidating the concept of postbiotics and their pivotal significance in mitigating various aspects of cardiovascular diseases. This review centers on a comprehensive examination of diverse SCFAs and their associated receptors, notably GPR41, GPR43, and GPR109a. In addition, we delve into the intricate cellular and pharmacological mechanisms through which these receptors operate, providing insights into their specific roles in managing cardiovascular conditions such as hypertension, atherosclerosis, heart failure, and stroke. The integration of current information in our analysis highlights the potential of both SCFAs and their receptors as a promising path for innovative therapeutic approaches in the field of cardiovascular health. The idea of postbiotics arises as an optimistic and inventive method, presenting new opportunities for preventing and treating cardiovascular diseases.

Cell-Specific mRNA Therapeutics for Cardiovascular Diseases and Regeneration.

Cardiovascular diseases (CVDs) represent a significant global health burden, demanding innovative therapeutic approaches. In recent years, mRNA therapeutics have emerged as a promising strategy to combat CVDs effectively. Unlike conventional small-molecule drugs, mRNA therapeutics enable the direct modulation of cellular functions by delivering specific mRNA molecules to target cells. This approach offers unprecedented advantages, including the ability to harness endogenous cellular machinery for protein synthesis, thus allowing precise control over gene expression without insertion into the genome. This review summarizes the current status of the potential of cell-specific mRNA therapeutics in the context of cardiovascular diseases. First, it outlines the challenges associated with traditional CVD treatments and emphasizes the need for targeted therapies. Subsequently, it elucidates the underlying principles of mRNA therapeutics and the development of advanced delivery systems to ensure cell-specificity and enhanced efficacy. Notably, innovative delivery methods such as lipid nanoparticles and exosomes have shown promise in improving the targeted delivery of mRNA to cardiac cells, activated fibroblasts, and other relevant cell types. Furthermore, the review highlights the diverse applications of cell-specific mRNA therapeutics in addressing various aspects of cardiovascular diseases, including atherosclerosis, myocardial infarction, heart failure, and arrhythmias. By modulating key regulatory genes involved in cardiomyocyte proliferation, inflammation, angiogenesis, tissue repair, and cell survival, mRNA therapeutics hold the potential to intervene at multiple stages of CVD pathogenesis. Despite its immense potential, this abstract acknowledges the challenges in translating cell-specific mRNA therapeutics from preclinical studies to clinical applications like off-target effects and delivery. In conclusion, cell-specific mRNA therapeutics have emerged as a revolutionary gene therapy approach for CVD, offering targeted interventions with the potential to significantly improve patient outcomes.

Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals of the general population with and without diabetes mellitus

Abstract Introduction Cardiovascular biomarkers may reflect different aspects of cardiovascular disease, including myocardial tissue damage (high-sensitive cardiac troponin [hs-cTn]), hemodynamic stress (N-terminal prohormone of brain natriuretic peptide [NT-proBNP)), or inflammation (high-sensitivity C-reactive protein [hs-CRP]). Purpose To determine the risk for fatal and non-fatal cardiovascular events in patients with diabetes mellitus (DM), a high-risk group for cardiovascular complications, after accounting for these biomarkers and to determine the risk associated with these biomarkers. Methods Harmonized data of population-based studies from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomaCaRE) and MOnica Risk, Genetics, Archiving and Monograph (MORGAM) consortia were used to calculate hazard ratios (HRs, 95% confidence intervals [CI] per standard deviation) for these biomarkers adjusted for diabetes, patient characteristics and biomarkers for their association with the primary endpoint of fatal and non-fatal cardiovascular events during a median follow-up of 9.6 years (maximum 28 years). Additionally, a years-of-life-lost analysis was conducted stratified by prevalent diabetes and specific biomarker cut-offs known to be associated with increased risk for events (hs-cTnI >5 ng/L, NTproBNP >125 ng/L, hs-CRP >5mg/L). Results We included 95,302 individuals, of whom 6,501 had DM (6.8%). Cox-regression analysis revealed DM to be independently associated with the primary endpoint (2.1 [95% CI 1.9, 2.3], p<0.001) despite adjustment for clinical characteristics and biomarkers. Also, all three biomarkers were independent predictors themselves: log-transformed NT-proBNP 1.3 [95% CI 1.3, 1.4] p<0.001; log-transformed hs-CRP 1.2 [95% CI 1.1, 1.2] p<0.001; third-root-transformed hs-cTnI 1.1 [95% CI 1.0, 1.1] p=0.0038). The sex-, age- and cohort-adjusted HR for the primary endpoint according to absolute biomarker concentrations derived by cox-regression models using cubic splines is provided for the three biomarkers in Figure 1. Upon dichotomization of biomarkers, individuals with diabetes and at least one elevated biomarker lost a median of 15.5 healthy years because of the primary endpoint (Kaplan-Meier plot in Figure 2, with age on the x-axis). Conclusion Our findings confirm that diabetes confers a residual cardiovascular risk beyond adjustment for clinical characteristics and cardiovascular biomarker. Furthermore, biomarkers may aid in the identification of patients at highest risk, which should be considered in future models of risk prediction. Funding Acknowledgement Type of funding sources: None.

Guidelines on models of diabetic heart disease.

Diabetes is a major risk factor for cardiovascular diseases, including diabetic cardiomyopathy, atherosclerosis, myocardial infarction, and heart failure. As cardiovascular disease represents the number one cause of death in people with diabetes, there has been a major emphasis on understanding the mechanisms by which diabetes promotes cardiovascular disease, and how antidiabetic therapies impact diabetic heart disease. With a wide array of models to study diabetes (both type 1 and type 2), the field has made major progress in answering these questions. However, each model has its own inherent limitations. Therefore, the purpose of this guidelines document is to provide the field with information on which aspects of cardiovascular disease in the human diabetic population are most accurately reproduced by the available models. This review aims to emphasize the advantages and disadvantages of each model, and to highlight the practical challenges and technical considerations involved. We will review the preclinical animal models of diabetes (based on their method of induction), appraise models of diabetes-related atherosclerosis and heart failure, and discuss in vitro models of diabetic heart disease. These guidelines will allow researchers to select the appropriate model of diabetic heart disease, depending on the specific research question being addressed.

Artificial Intelligence and Machine Learning Based Models for Prediction and Treatment of Cardiovascular Diseases: A Review

Advances in Machine Learning (ML) algorithms, computing and Artificial Intelligence (AI)-based systems have been gradually finding applications in several domains including medical and health care systems. By using big data analytics and machine learning methodologies, AI has become a promising tool in the diagnosis and treatment of cardiovascular diseases. AI-ML based applications enhance our understanding of different parameters and phenotypes of heart diseases and lead to newer therapeutic strategies to tackle different types of cardiovascular ailments, a newer approach to cardiovascular drug therapy and a post-marketing survey of prescription drugs. Although AI has wide range of applications, it is in infant stage and has certain limitations in the clinical use of results and their interpretations such as data privacy, selection bias etc, which may result in wrong conclusions. Thus, AI-ML is a transformative technology and has immense potential in health care systems. This review covers various aspects of cardiovascular diseases (CVDs) and illustrate AI and ML based methods including supervised, unsupervised and deep learning and their applications in cardiovascular imaging, cardiovascular risk prediction and newer drug targets.

(-)-Epicatechin Improves Vasoreactivity and Mitochondrial Respiration in Thermoneutral-Housed Wistar Rat Vasculature.

Cardiovascular disease (CVD) is a global health concern. Vascular dysfunction is an aspect of CVD, and novel treatments targeting vascular physiology are necessary. In the endothelium, eNOS regulates vasodilation and mitochondrial function; both are disrupted in CVD. (–)-Epicatechin, a botanical compound known for its vasodilatory, eNOS, and mitochondrial-stimulating properties, is a potential therapy in those with CVD. We hypothesized that (–)-epicatechin would support eNOS activity and mitochondrial respiration, leading to improved vasoreactivity in a thermoneutral-derived rat model of vascular dysfunction. We housed Wistar rats at room temperature or in thermoneutral conditions for a total of 16 week and treated them with 1mg/kg body weight (–)-epicatechin for 15 day. Vasoreactivity, eNOS activity, and mitochondrial respiration were measured, in addition to the protein expression of upstream cellular signaling molecules including AMPK and CaMKII. We observed a significant improvement of vasodilation in those housed in thermoneutrality and treated with (–)-epicatechin (p < 0.05), as well as dampened mitochondrial respiration (p < 0.05). AMPK and CaMKIIα and β expression were lessened with (–)-epicatechin treatment in those housed at thermoneutrality (p < 0.05). The opposite was observed with animals housed at room temperature supplemented with (–)-epicatechin. These data illustrate a context-dependent vascular response to (–)-epicatechin, a candidate for CVD therapeutic development.

Review on bisphenol A and the risk of polycystic ovarian syndrome: an insight from endocrine and gene expression.

Bisphenol A (BPA) is one of the most widely studied endocrine disrupting chemicals because of its structural similarity to 17-β estradiol; its ability to bind as an agonist/antagonist to estrogen receptors elicits adverse effects on the functioning of the metabolic and endocrinal system. Therefore, BPA has been thoroughly scrutinized concerning its disruption of pathways like lipid metabolism, steroidogenesis, insulin signaling, and inflammation. This has resulted in reports of its correlation with various aspects of cardiovascular diseases, obesity, diabetes, male and female reproductive disorders, and dysfunctions. Among these, the occurrence of the polycystic ovarian syndrome (PCOS) in premenopausal women is of great concern. PCOS is a highly prevalent disorder affecting women in their reproductive age and is clinically characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, along with metabolism-related dysfunctions like hyperinsulinemia, obesity, and insulin resistance. In this review, we analyzed certain researched effects of BPA, while focusing on its ability to alter the expression of various significant genes like GnRH, AdipoQ, ESR1, StAR, CYP11A1, CYP19A1, and many more involved in the pathways and endocrine regulation, whose disruption is commonly associated with the clinical manifestations of PCOS.

Role of BPIFB4 in Immune System and Cardiovascular Disease: the Lesson from Centenarians

Recent discoveries have shed light on the participation of the immune system in the physio pathology of the cardiovascular system underpinning the importance of keeping the balance of the first to preserve the latter. Aging, along with other risk factors, can challenge such balance triggering the onset of cardiovascular diseases. Among several mediators ensuring the proper cross-talk between the two systems, bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been shown to have a pivotal role, also by sustaining important signals such as eNOS and PKC-alpha. In addition, the Longevity-associated variant (LAV), which is an haplotype allele in BPIFB4characterized by 4 missense polymorphisms, enriched in homozygosity in Long Living Individuals (LLIs), has been shown to be efficient, if administered systemically through gene therapy, in improving many aspects of cardiovascular diseases (CVDs). This occurs mainly through a fine immune system remodeling across: 1) a M2 macrophage polarizing effect, 2) a favorable redistribution of the circulating monocyte cell subsets and 3) the reduction of T-cell activation. Furthermore, LAV-BPIFB4 treatment induced a desirable recovery of the inflammatory balance by mitigating the pro-inflammatory factor levels and enhancing the anti-inflammatory boost through a mechanism that is partially dependent on SDF-1/CXCR4 axis. Importantly, the remarkable effects of LAV-BPIFB4 treatment, which translates in increased BPIFB4 circulating levels, mirror what occurs in long-living individuals (LLIs) in whom the high circulating levels of BPIFB4 are protective from age-related and CVDs and emphasize the reason why LLIs are considered a model of successful aging. Here, we review the mechanisms by which LAV-BPIFB4 exerts its immunomodulatory activity in improving the cardiovascular-immune system dialogue that might strengthen its role as a key mediator in CVDs.

Prevention continuum: an assessment of cardiovascular disease prevention based on the data from a survey of doctors

Aim. To assess the awareness and engagement of health professionals in Russia in the main aspects of cardiovascular disease prevention.Material and methods. In order to assess engagement and awareness, an online survey of Russian primary health care providers was conducted in March 2021. The survey was conducted using original questionnaire, which includes the main questions aimed at early identification of patients with modifiable cardiovascular risk factors.Results. In case of newly diagnosed hypercholesterolemia and elevated blood pressure during screening, 91,8% (n=458) of the surveyed medical specialists record the results and immediately consult the patient on these issues. Similar responses was obtained by 93% (n=464) of doctors for patients with previously prescribed antihypertensive and/or lipid-lowering therapy. In addition, 46,5% (n=232) responded that during screening, 10-30% of patients had newly diagnosed hypertension and/or total cholesterol &gt;5 mmol/L. A total of 28,9% (n=144) of respondents noted that 30-50% of patients with newly diagnosed hypertension and/or total cholesterol &gt;5 mmol/L are detected at screening. It is noteworthy that 41,9% (n=209) of physicians devote 1 to 5 minutes to a patient, describing the changes in lifestyle, diet and physical activity. For 35,1% (n=175) of the respondents, this takes from 5 to 10 minutes, 22% (n=110) — &gt;10 minutes, while ~5 respondents refer patients to another specialist for this purpose.Conclusion. The survey showed a high awareness of medical specialists in the need to monitor and modify risk factors. However, ~40% of surveyed doctors do not devote enough time to explaining issues of modifying lifestyle, diet and physical activity.

Abstract 12672: A New Genetic Model Organism for Primate-Specific Cardiac Function and Disease

Introduction: Due to differences in cardiac structure and function, it has become increasingly clear that many aspects of cardiovascular disease are not well modeled in mice. This has spurred a search for new model organisms with the practical advantages of mice but that more closely mimic human biology. This study examines mouse lemur (Microcebus species) - the world’s smallest, most prolific, and among the most abundant non-human primates - and the cheapest and easiest to maintain, as such a model. Methods: This study characterizes the normal cardiac anatomy and histology, and baseline values for heart rate, cholesterol, and cardiac waveform by ECG (a point-of-care blood assay and a portable 3-lead monitoring device were used to screen ~400 animals). It also describes the development of a whole genome and single cell RNA-sequencing and analysis pipeline for Microcebus murinus. Results: Transcriptomic analysis identified 6000 cardiac cells, including all major and many minor cardiac cell types, including several exceedingly rare cell types. The lipid profiles of these animals more closely resembled that of humans, with an average LDL level of 81 mg/dL, with several obese animals having values &gt;200. 20 naturally-occurring ECG variants were identified, all resembling known human ECG variants including 8 major cardiac arrhythmias. The screen uncovered the first cases of heart disease in lemurs. One is atrial fibrillation; Another is sick sinus syndrome (SSS), whose human familial form arises from mutations in ion channel genes, HCN4 or SCN5A. Both arrythmias show familial clustering, with the SSS pedigree exhibiting an autosomal dominant inheritance pattern. SNP/variant analysis revealed 30 million variants in the SSS animals, and ongoing work has narrowed these to just a handful of high impact, functional variants in SCN5A, suggesting that the underlying mouse lemur SSS disease gene and causative mutation are the same as in humans. Conclusions: The results establish the mouse lemur as the first systematic, high-throughput primate genetic model for cardiovascular physiology and disease, and reveal human-like cardiac cell types and diseases. The approach uncovered naturally-occurring cardiac diseases that have not been found in mice.

Insight into Shenqi Jiangtang Granule on the improved insulin sensitivity by integrating in silico and in vivo approaches

Ethnopharmacological relevancePresently, insulin resistance has been a growing concern that urgently needs to be addressed, because it not only places patients at risk of developing type 2 diabetes mellitus but also results in metabolic syndrome and different aspects of cardiovascular diseases. Shenqi Jiangtang Granule (SJG) is a classic traditional Chinese medicine (TCM) prescription that is widely used to treat diabetes mellitus and its complications in clinical practice. While studies have revealed that SJG with multi-ingredients and multi-targets characteristics possesses potential anti-insulin resistance pharmacological properties, its mechanisms of action and molecular targets for the treatment of insulin resistance are still obscure, which prompt us to conduct an in-depth research. Aim of the studyThis study was purposed to uncover the pharmacological mechanism of SJG against insulin resistance through integrating network pharmacology and experimental validation. Materials and methodsThe putative ingredients of SJG and its related targets were discerned from the TCMSP database. Subsequently, insulin resistance-associated targets were retrieved from GeneCard, OMIM, and GEO database. Compound-target, protein-protein interaction (PPI), and compound-target-pathway networks were established using Cytoscape software. GO and KEGG pathway analyses were performed to identify possible enrichment of genes with specific biological themes. Molecular docking was used to verify the correlation between the main active ingredients and hub targets. Optimal docking conformation was further analyzed by molecular dynamics (MD) simulation. Finally, the potential molecular mechanisms of SJG acting on insulin resistance, as predicted by the network pharmacology analyses, were validated experimentally in insulin-resistant rat model. Results136 active compounds, 211 corresponding targets in addition to 1463 disease-related targets were collected, of which 94 intersection targets were obtained. 29 key targets including AKT1, VEGFA, IL-6, CASP3, and PTGS2 were identified through PPI network analysis. Hub module of PPI network was closely associated with inflammation. GO and KEGG analyses also revealed that inflammation-related pathways may be a central factor for SJG to modulate insulin resistance. Molecular docking test showed a good binding potency between primary active ingredients and core targets, and the binding mode of optimal docking conformation was stable in MD simulation. A rat model of insulin resistance was successfully induced by chronic high-fat diet (HFD) consumption. Through a series of in vivo studies, including HEC, ITT, and HOMA-IR measurement, it was revealed that SJG exhibited a beneficial effect on ameliorating insulin resistance, as demonstrated by a significant increase of GIR and a significant decrease of AUCITT and HOMA-IR index value. Further molecular biological analysis showed that SJG can decrease the mRNA expression level and serum concentration of inflammatory cytokines (TNF-α, IL-6, and IL-1β), along with suppressing the p-NFκB protein overexpression, indicating its anti-inflammatory activity. Also, it can contribute to the reversal of the impaired hepatic insulin signaling pathway, as evidenced by up-regulated protein expression of p-Akt and GLUT2. ConclusionsThrough in silico and in vivo approaches, the present study not only provides a unique insight into the possible mechanism of SJG in insulin resistance after successfully filtering out associated key target genes and signaling pathways, but also suggests a novel promising therapeutic strategy for curing insulin resistance.

Abstract P069: White Cell Gene Expression Related To Immune Function And Cumulative Blood Pressure During Young Adulthood And Middle Age: Coronary Artery Risk Development In Young Adults (CARDIA)

Introduction: High blood pressure (BP) is a global public health problem that is strongly associated with many aspects of cardiovascular disease. Approximately 90% of hypertension cases have unknown cause. Studies of white blood cell gene expression may help to clarify the pathobiology. Methods: Gene expression (25 genes) was assayed in CARDIA at the Year 25 Exam (N=3,074 black and white men and women in 4 US cities, examined in 2010-2011, age 42-56 years). Whole blood was collected in PAXgene Blood RNA tubes; mRNA was isolated using the PAXgene Blood RNA kit (Qiagen Inc., Germantown, MD). The nCounter analysis system (Nanostring Inc., Seattle, WA) was used to measure expression of 25 genes related to inflammation and oxidative stress. Gene expression levels were logarithmically (base 2) transformed to approximate a normal distribution, so 1 unit higher represents doubling of the expression. Average cumulative sitting rest BP exposure was calculated (N=2,823) as the time weighted average across ≥5 BP measurements among 9 CARDIA exams with ≥1 measurement in each of Set 1 Years 0, 2, 5, 7; Set 2 Years 10, 15; and Set 3 Years 20, 25, 30. We added 10 mmHg to the systolic BP and 5 mmHg to the diastolic BP at visits in which antihypertensive medications were used. Linear regression estimated associations between dependent variables cumulative systolic and diastolic BP and each of the 25 gene expression levels, adjusting for age, race, sex, clinic, and year 25 body mass index. Hypertension at year 25 was defined as BP &gt;140/90 mmHg or taking antihypertensive medications and pre-hypertension at year 25 was defined as BP between 121-139/81-90 mmHg, not taking antihypertensive medications. Unconditional logistic regression models were used to estimate the cross sectional association between hypertension and gene expression after adjusting for the covariates mentioned above. Results: The mean ± standard deviation for cumulative systolic BP was 113±11 mm Hg and for cumulative diastolic BP was 72±8 mmHg. NADH Dehydrogenase [Ubiquinone] 1 Beta Subcomplex Subunit 3 ( NDUFB3) , a mitochondrial gene involved in the electron transport chain was significantly associated with both cumulative systolic (β=1.549; p&lt;0.0001) and diastolic BP measures (β=1.281 mmHg/1 log 2 unit of expression; p&lt;0.0001), even after Bonferroni correction. Other genes had weaker signals. Consistent with these observations, hypertension (n=898) at year 25 (OR: 1.737; p&lt;0.001) and pre-hypertension (n=1,127) at year 25 (OR:1.288; p=0.005) were also associated with increased NDUFB3 expression. Conclusions: Expression of the NDUFB3 gene, an element of oxidative stress, was associated with BP assessed throughout young adult and middle age and with concurrent hypertension.

The effect of omega-3 fatty acids on a biomarker of head trauma in NCAA football athletes: a\xa0multi-site, non-randomized study

BackgroundAmerican-style football (ASF) athletes are at risk for cardiovascular disease (CVD) and exhibit elevated levels of serum neurofilament light (Nf-L), a biomarker of axonal injury that is associated with repetitive head impact exposure over the course of a season of competition. Supplementation with the w-3 fatty acid (FA) docosahexaenoic acid (DHA) attenuates serum Nf-L elevations and improves aspects of CVD, such as the omega-3 index (O3I). However, the effect of combining the w-3 FA eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) with DHA on, specifically, serum Nf-L in ASF athletes is unknown. Therefore, this study assessed the effect of supplemental w-3 FA (EPA+DPA+DHA) on serum Nf-L, plasma w-3 FAs, the O3I, and surrogate markers of inflammation over the course of a season.MethodsA multi-site, non-randomized design, utilizing two American football teams was employed. One team (n = 3 1) received supplementation with a highly bioavailablew-3 FA formulation (2000mg DHA, 560mg EPA, 320mg DPA, Mindset®, Struct Nutrition, Missoula, MT) during pre-season and throughout the regular season, while the second team served as the control (n = 35) and did not undergo supplementation. Blood was sampled at specific times throughout pre- and regular season coincident w ith changes in intensity, physical contact, and changes in the incidence and severity of head impacts. Group differences were determined via a mixed-model between-within subjects ANOVA. Effect sizes were calculated using Cohen’s dfor all between-group differences. Significance was set a priori at p< .05.ResultsCompared to the control group, ASF athletes in the treatment group experienced large increases in plasma EPA (p < .001, d = 1.71) and DHA (p < .001, d = 2.10) which contributed to increases in the O3I (p < .001, d = 2.16) and the EPA:AA ratio (p = .001, d = 0.83) and a reduction in the w-6: w-3 ratio (p < .001, d = 1.80). w-3 FA supplementation attenuated elevations in Nf-L (p = .024). The control group experienced a significant increase in Nf-L compared to baseline at several measurement time points (T2, T3, and T4 [p range < .001 – .005, drange = 0.59-0.85]).ConclusionsThese findings suggest a cardio- and neuroprotective effect of combined EPA+DPA+DHA w-3 FA supplementation in American-style football athletes.Trial registrationThis trial was registered with the ISRCTN registry (ISRCTN90306741).

TRPC5 in cardiovascular diseases.

Cardiovascular diseases (CVD), especially acute myocardial infarction, are the leading cause of death, morbidity and disability across the world, affecting millions of people each year. Atherosclerosis (AS) is the major cause of CVD, and is a chronic inflammation involving different cell types and various molecular mechanisms. Ca2+ dynamics of endothelial cells (ECs) and smooth muscle cells (SMCs) exert a significant influence on many aspects of CVD. Transient receptor potential channel 5 (TRPC5) is a member of the transient receptor potential (TRP) channels, which consists of a large number of nonselective cation channels with variable degrees of Ca2+-permeability. As a Ca2+-permeable cation channel, Human TRPC5 is expressed in a number of cell types, including ECs and muscle cells, as well as lungs and kidneys. TRPC5 is involved in renal, tumorous, neuronal and vascular diseases. In recent years, the roles of TRPC5 in CVD have been widely implicated in various disorders, such as AS, cardiac hypertrophy and blood pressure regulation. The TRPC5 mechanism of action may be associated with regulation of calcium homeostasis, oxidative stress and apoptosis. In this review, we highlight the significant roles of TRPC5 in the heart, and evaluate the potential of therapeutics targets which block TRPC5 for the treatment of CVD and related diseases.

The Role of BPIFB4 in Immune System and Cardiovascular Disease: The Lesson from Centenarians.

Recent discoveries have shed light on the participation of the immune system in the physio pathology of the cardiovascular system underpinning the importance of keeping the balance of the first to preserve the latter. Aging, along with other risk factors, can challenge such balance triggering the onset of cardiovascular diseases. Among several mediators ensuring the proper cross-talk between the two systems, bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been shown to have a pivotal role, also by sustaining important signals such as eNOS and PKC-alpha. In addition, the Longevity-associated variant (LAV), which is an haplotype allele in BPIFB4 characterized by 4 missense polymorphisms, enriched in homozygosity in Long Living Individuals (LLIs), has been shown to be efficient, if administered systemically through gene therapy, in improving many aspects of cardiovascular diseases (CVDs). This occurs mainly through a fine immune system remodeling across: 1) a M2 macrophage polarizing effect, 2) a favorable redistribution of the circulating monocyte cell subsets and 3) the reduction of T-cell activation. Furthermore, LAV-BPIFB4 treatment induced a desirable recovery of the inflammatory balance by mitigating the pro-inflammatory factor levels and enhancing the anti-inflammatory boost through a mechanism that is partially dependent on SDF-1/CXCR4 axis. Importantly, the remarkable effects of LAV-BPIFB4 treatment, which translates in increased BPIFB4 circulating levels, mirror what occurs in long-living individuals (LLIs) in whom the high circulating levels of BPIFB4 are protective from age-related and CVDs and emphasize the reason why LLIs are considered a model of successful aging. Here, we review the mechanisms by which LAV-BPIFB4 exerts its immunomodulatory activity in improving the cardiovascular-immune system dialogue that might strengthen its role as a key mediator in CVDs.

AMP-activated protein kinase regulates expression of macrophage migration inhibitory factor and MIR-18A in HUVEC

Background and Aims: Macrophage migration inhibitory factor (MIF) has pleiotropic immune functions in a number of inflammatory diseases. Recent evidence from expression and functional studies has indicated that MIF is involved in various aspects of cardiovascular disease and autophagy. AMP-activated protein kinase (AMPK) plays role in maintaining cellular energy homeostasis. Previous studies showed that dysregulation of autophagy and decreased AMPK activity lead to atherosclerosis. In addition, it was shown that miR-18a is a regulator of autophagy and related with atherosclerosis associated genes. The aim of this study was to determine the expression of atherosclerosis related miR-18a and MIF gene and to test the dependence of their expression on AMPK activity in HUVEC.

Integrated Network Pharmacology Analysis and Experimental Validation to Reveal the Mechanism of Anti-Insulin Resistance Effects of Moringa oleifera Seeds.

Background and PurposeInsulin resistance (IR) is one of the factors that results in metabolic syndrome, type 2 diabetes mellitus and different aspects of cardiovascular diseases. Moringa oleifera seeds (MOS), traditionally used as an antidiabetic food and traditional medicine in tropical Asia and Africa, have exhibited potential effects in improving IR. To systematically explore the pharmacological mechanism of the anti-IR effects of MOS, we adopted a network pharmacology approach at the molecular level.MethodsBy incorporating compound screening and target prediction, a feasible compound-target-pathway network pharmacology model was established to systematically predict the potential active components and mechanisms of the anti-IR effects of MOS. Biological methods were then used to verify the results of the network pharmacology analysis.ResultsOur comprehensive systematic approach successfully identified 32 bioactive compounds in MOS and 44 potential targets of these compounds related to IR, as well as 37 potential pathways related to IR. Moreover, the network pharmacology analysis revealed that glycosidic isothiocyanates and glycosidic benzylamines were the major active components that improved IR by acting on key targets, such as SRC, PTPN1, and CASP3, which were involved in inflammatory responses and insulin-related pathways. Further biological research demonstrated that the anti-IR effects of MOS were mediated by increasing glucose uptake and modulating the expression of SRC and PTPN1.ConclusionOur study successfully predicts the active ingredients and potential targets of MOS for improving IR and helps to illustrate mechanism of action at a systemic level. This study not only provides new insights into the chemical basis and pharmacology of MOS but also demonstrates a feasible method for discovering potential drugs from traditional medicines.

Hypertensive patients\u2019 knowledge of cardiovascular disease in Calabar, Nigeria

BackgroundThis study aimed at assessing knowledge of cardiovascular disease risk factors and prevention, among hypertensive patients in a developing country setting with high cardiometabolic disease morbidity and mortality.MethodsUsing descriptive cross-sectional study design and random sampling method, a 30-item questionnaire was used to obtain quantitative data on knowledge of key aspects of cardiovascular disease and practice of preventive measures among hypertensive patients in Calabar.ResultTwo hundred and twelve (212) respondents were surveyed with mean age of 45.5 ± 10.8 years. Approximately two-thirds of respondents (67.9%) had unsatisfactory level of knowledge of CVD. Most respondents had unsatisfactory level of knowledge of appropriate diet (77.4%), basic epidemiology (80.2%), risk factors (63.2%), and symptoms of CVD (74.5%). The mean score for knowledge of risk factors was significantly higher among females compared with males (p < 0.05). Consumers compared with non-consumers of alcohol had significantly lower mean scores for knowledge of appropriate diet and symptoms of CVD (p < 0.05). Except for medical knowledge where mean score of knowledge was significantly higher among respondents occasionally exercised or consumed fresh fruits compared with other groups, there was no significant difference in mean score of knowledge for other components comparing the various categories of active exercise and consumption of fresh fruits (p > 0.05).ConclusionUnsatisfactory level of knowledge of cardiovascular disease among hypertensive patients in the study setting was high. There is urgent need to improve efforts and strategies for health education and counseling of patients toward sustainable adoption of preventive behaviors.

Place des produits laitiers fermentés dans le traitement des maladies cardio-vasculaires

Fermented milk products have nutritional qualities that could preserve cardiovascular health. While the benefits of yoghurt are highlighted by epidemiological and clinical studies, there is a lack of evidence for other fermented dairy products. In order to better identify their effects, work targeting specific aspects of cardiovascular disease is needed.

Cardiovascular Diseases (CVDs) in COVID-19 Pandemic Era.

Introduction:COVID-19 is the disease caused by an infection of the SARS-CoV-2 virus, previously known as 2019 Novel Coronavirus (2019-nCoV) respiratory disease. World Health Organization (WHO) declared the official name as COVID-19 in February 2020 and in 11th March 2020 declared COVID-19 as Global Pandemic. In June 6th 2020, over 7 million cases registered in the world, recovered 3.4 million and death over 402.000.Aim:The aim of this study is to retreive published papers about COVID-19 infection deposited in PubMed data base and analyzed current results of investigations regarding morbidity and mortality rates as consequences of COVID-19 infection and opinions of experts about treatment of afected patients with COVID-19 who have Cardiovascular diseases (CVDs).Methods:It’s used method of descriptive analysis of the published papers with described studies about Corona virus connected with CVDs.Results:After searching current scientific literature (on PubMed till today is deposited more than 1.000 papers about COVID-19 with consequences in almost every medical disciplines), we have acknowledged that till today not any Evidence Based Medicine (EBM) study in the world. Also, there are no unique proposed ways of treatments and drugs to protect patients, especially people over 65 years old, who are very risk group to be affected with COVID-19, including patients with CVDs. Vaccine against COVID-19 is already produced and being in phases of testing in praxis in treatment of COVID-19 at affected patients, but the opinions of experts and common people whole over the world about vaccination are full of controversis.Conclusion:Frequent hand washing, avoiding crowds and contact with sick people, and cleaning and disinfecting frequently touched surfaces can help prevent coronavirus infections are the main proposal of WHO experts in current Guidelines, artefacts stored on a web site. Those preventive measures at least can help to everybody, including also the patients who have evidenced CVDs in their histories of illness. Authors analyzed most important dilemmas about all aspects of CVDs, including etipathogenesis, treatment with current drugs and use of potential discovered vaccines against COVID-19 infection, described in scientific papers deposited in PubMed data base.