Atherosclerosis-related Cardiovascular Diseases Research Articles

Understanding the Complex Interplay of Epigenetic Factors in Atherosclerosis: A Review

This review focuses on the epigenetic factors that play a vital role in the formation of plaques and lead to atherosclerosis and related diseases in humans during current times. Apart from the epigenetics there are plenty more factors that influence the atherosclerotic risk in the older population of the current era. Lack of physical activities has become one of the most commonly found traits that causes obesity in people especially the middles aged adults. People working 9 - 5 in an office, or an IT firm tend spend idle time with their computer for 4 - 5 consecutive hours with barely changing their position. Lack of exercise tends to affect not only the physical health but also stress a person mentally. Chronic inflammatory diseases like atherosclerosis have a major role in the morbidity and mortality from cardiovascular disease worldwide. Atherosclerotic plaques are created by the pathophysiological process of lipids, inflammatory cells and fibrous components gradually accumulating within artery walls. Endothelial dysfunction signals the start of atherosclerosis and allows low-density lipoproteins (LDL) to enter the subendothelial region. Oxidative stress-induced changes in retained low-density lipoprotein (LDL) set off an inflammatory cascade that draws T cells and monocytes to the site of the lesion. The interaction of these immune cells with the local vascular cells encourages the production of foam cells, which fills the plaque’s centre with lipids. Smooth muscle cells multiply and help produce fibrous caps as the lesion ages, which affects the stability of the plaque. Studies shows how the brain responds to physical labour and how differently the effectively the enzymes and hormones are secreted, and their actions are vastly guided based on the physical stress an individual undergoes. Among the most prominent causes of atherosclerosis epigenetics has been focussed majorly in this review, where we focus on the underlying genetic factors that play a vital role in atherosclerosis and related cardiovascular diseases and also the genetic approach to a treatment is also elaborated. A number of miRNAs are involved in the cause/cure for the atherosclerosis, the following tables give an outlook regarding the same. This review aims to focus on the causes, risk factors, pathophysiology and the treatment and therapies that are currently available all the way concentrating on the genetic approach in the above-mentioned perspective. HIGHLIGHTS The review revolves around the modifiable and non-modifiable risk factors leading to atherosclerosis. Key risk factors and epigenetics causes of atherosclerosis and atherosclerosis related Cardio vascular Diseases (CVD). The article explains in detail regarding the pathophysiology of atherosclerosis. The progression and stages of atherosclerosis. GRAPHICAL ABSTRACT

Life cycle of macrophages in atherosclerotic inflammation progression and resolution: mediators and interventions (narrative review)

Abstract As one of the pathological causes of coronary heart disease, atherosclerosis poses a major threat to human health. Macrophages play an important role in regulating atherosclerotic disease progression. Specifically, atherosclerotic inflammation is initiated when low-density lipoproteins infiltrate the subcutaneous area and are phagocytosed by macrophages, leading to foam cell formation. The subsequent inflammation progression or resolution depends on the delicate balance between proinflammatory and anti-inflammatory mediators. In cases where proinflammatory factors dominate, macrophages tend to activate the pyroptosis and necrosis pathways, resulting in the release of intracellular damage-associated molecular patterns and promoting necrotic core formation and plaque progression. Conversely, when anti-inflammatory factors prevail, macrophages engage in autophagy-mediated intracellular lipid metabolism while inhibiting inflammation progression through the efferocytosis of apoptotic cells. The regulatory function of macrophages in atherosclerosis can also be understood from the perspective of their life cycles. Lipid retention within the arterial intima and its subsequent uptake by macrophages are the characteristic pathological hallmarks of atherosclerosis. As pivotal effector cells in this process, macrophages with their distinctive performances decisively determine the progression and resolution of atherosclerotic inflammation. The complete life cycle of macrophages in atherosclerotic plaques encompasses chemotaxis, infiltration, polarization, uptake of lipoproteins for metabolic efflux, foam cell formation, lipid overload, and various forms of programmed necrosis, including autophagy, pyroptosis, apoptosis, necrosis, and efferocytosis, to facilitate the removal of apoptotic macrophages and limit inflammation progression. The behavior of macrophages in atherosclerosis has rarely been comprehensively addressed in previous review articles. This article provides an extensive overview of the entire life cycle of macrophages following their response to atherosclerotic inflammation and the impact of regulatory factors on inflammation progression and resolution. Considering that macrophages play a pivotal role in the inflammatory response associated with atherosclerosis, targeting the regulation of their life cycle holds promise for therapeutic interventions against atherosclerosis-related cardiovascular diseases.

Gender characteristics of the prevalence of noncommunicable diseases in the adult population of the Vladimir region

Aim. To assess the prevalence of major noncommunicable diseases (NCDs) taking into account gender characteristics in a random sample of adults in 5 cities of the Vladimir region.Material and methods. This cross-sectional population-based study (May 2018 — March 2020) included 1350 people (men and women aged 30-69 years) from 5 cities of the Vladimir region. The response rate was 87%. A total of 1174 people completed the study. Of these, 424 (36,1%) were men and 750 (63,9%) women. Respondents were surveyed using a standard questionnaire prepared by the National Medical Research Center for Therapy and Preventive Medicine, which included socio-demographic characteristics, behavioral risk factors, data on somatic diseases and medications taken.Results. The prevalence of coronary artery disease among men was 14,1%, among women — 9,5% (p=0,016). In men, the second most common disease is chronic obstructive pulmonary disease (COPD), which was 2,5 times more common than in women — 10,6 and 4,5%, respectively (p=0,001). Among women, the second most common disease was type 2 diabetes (T2D), accounting for 7,6%. Cerebrovascular diseases occupy fourth place in the NCD structure. Their prevalence was 6,1% among men and 4,4% among women. Cancer diseases were less common than other chronic diseases without sex differences — 2,8 and 3,1%, respectively. In certain cities, the prevalence of NCDs varied. Every third man and fourth women had a positive family history for cardiovascular diseases (CVDs) (p=0,005). About 20% of men reported a positive family history for COPD, while among women this figure was 2 times lower (p=0,001). Men and women were comparable in terms a family history for T2D — 10,4 and 12,5%, respectively. A positive family history for tumors of various locations was recorded in ~5%.Conclusion. In the adult working-age population of the Vladimir region, atherosclerosis-related CVDs was identified in 17% of cases. The incidence of T2D and COPD in the adult population was approximately the same and amounted to >7%. The prevalence of cancer was 3%. Sex differences were identified in the prevalence of coronary artery disease and COPD.

Short-Term Effect of Nutraceutical Fruit Juices on Lipid Metabolism in Patients with Acquired Hypercholesterolemia.

The crucial role of dyslipidaemia, especially hypercholesterolemia, in the development of atherosclerosis-related cardiovascular diseases has been extensively documented in genetic, pathologic, observational and intervention studies. The European guidelines for dyslipidaemia management include the possible use of lipid-lowering nutraceuticals to support a relatively large number of natural compounds. In this context, we have conducted a study to investigate whether dietary supplementation with a functional nutraceutical beverage, containing a standardized polyphenolic fraction from fruit, red yeast rice, phytosterols, and berberine complexed with β-cyclodextrin, could positively affect serum lipid concentration in 14 subjects with hypercholesterolemia. After 12 weeks of treatment, dietary supplementation with this nutraceutical combination was associated with significant improvements in total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B, compared to baseline. Compliance was excellent and no adverse effects were reported. In conclusion, this study demonstrates that 100 mL of a functional beverage containing lipid-lowering nutraceuticals safely leads to significant improvements in serum lipids in subjects with moderate hypercholesterolemia. Future research is needed to unravel the role that the polyphenols contained in fruit extracts play in the reduction of cholesterolemia and in cardiovascular disease prevention.

Hippo/YAP signaling pathway: a new therapeutic target for diabetes mellitus and vascular complications.

Diabetic angiopathy, which includes diabetic kidney disease (DKD), cardio-cerebrovascular disease, and diabetic retinopathy (DR) among other diseases, is one of the most common complications affecting diabetic patients. Among these, DKD, which is a major cause of morbidity and mortality, affects about 40% of diabetic patients. Similarly, DR involves retinal neovascularization and neurodegeneration as a result of chronic hyperglycemia and is the main cause of visual impairment and blindness. In addition, inflammation also promotes atherosclerosis and diabetes, with atherosclerosis-related cardiovascular diseases being often a main cause of disability or death in diabetic patients. Given that vascular diseases caused by diabetes negatively impact human health, it is therefore important to identify appropriate treatments. In this context, some studies have found that the Hippo/Yes-associated protein (YAP) pathway is a highly evolutionarily conserved protein kinase signal pathway that regulates organ growth and size through its effector signaling pathway Transcriptional co-Activator with PDZ-binding motif (TAZ) and its YAP. YAP is a key factor in the Hippo pathway. The activation of YAP regulates gluconeogenesis, thereby regulating glucose tolerance levels; silencing the YAP gene thereby prevents the formation of glomerular fibrosis. YAP can combine with TEA domain family members to regulate the proliferation and migration of retinal vascular endothelial cells (ECs), so YAP plays a prominent role in the formation and pathology of retinal vessels. In addition, YAP/TAZ activation and translocation to the nucleus promote endothelial inflammation and monocyte-EC attachment, which can increase diabetes-induced cardiovascular atherosclerosis. Hippo/YAP signaling pathway provides a potential therapeutic target for diabetic angiopathy, which can prevent the progression of diabetes to DR and improve renal fibrosis and cardio-vascular atherosclerosis.

Exploring the difference in the mechanics of vascular smooth muscle cells from wild-type and apolipoprotein-E knockout mice.

Atherosclerosis-related cardiovascular diseases are a leading cause of mortality worldwide. Vascular smooth muscle cells (VSMCs) comprise the medial layer of the arterial wall and undergo phenotypic switching during atherosclerosis to a synthetic phenotype capable of proliferation and migration. The surrounding environment undergoes alterations in extracellular matrix (ECM) stiffness and composition and an increase in cholesterol content. Using an atherosclerotic murine model, we analyzed how the mechanics of VSMCs isolated from Western diet-fed apolipoprotein-E knockout (ApoE-/-) and wild-type (WT) mice were altered during atherosclerosis. Increased stiffness of ApoE-/- VSMCs correlated with a greater degree of stress fiber alignment, as evidenced by atomic force microscopy (AFM)-generated force maps and stress fiber topography images. On type-1 collagen (COL1)-coated polyacrylamide (PA) gels (referred to as substrate) of varying stiffness, ApoE-/- VSMCs had lower adhesion forces to COL1 and N-cadherin (N-Cad) compared with WT cells. ApoE-/- VSMC stiffness was significantly greater than that of WT cells. Cell stiffness increased with increasing substrate stiffness for both ApoE-/- and WT VSMCs. In addition, ApoE-/- VSMCs showed an enhanced migration capability on COL1-coated substrates and a general decreasing trend in migration capacity with increasing substrate stiffness, correlating with lowered adhesion forces as compared with WT VSMCs. Altogether, these results demonstrate the potential contribution of the alteration in VSMC mechanics in the development of atherosclerosis.

The association between genetic markers from gwas and essential hypertension in a case-control study (Siberian population)

Background and Aims : Hypertension is a major risk factor for atherosclerosis-related cardiovascular diseases (ACVD) and a multifactorial condition with genetic susceptibility. In a case-control study we investigated the association between essential hypertension (HT) and blood pressure (BP) and a number of single nucleotide polymorphisms (SNPs) identified in GWAS.

Comparative safety and efficacy of low- or moderate-intensity statin plus ezetimibe combination therapy and high-intensity statin monotherapy: A meta-analysis of randomized controlled studies.

Statin is highly recommended for dyslipidemia to prevent atherosclerosis-related cardiovascular diseases and death. The aim of this study was to compare the efficacies and safeties of low/moderate-intensity statin plus ezetimibe combination therapy vs. high-intensity statin monotherapy. Meta-analysis was conducted on data included in published studies performed to compare the effects of the two treatments on lipid parameters and hs-CRP. Safety-related parameters were also evaluated. Eighteen articles were included in the meta-analysis. In terms of efficacy, low/moderate-intensity statin plus ezetimibe reduced LDL-C (SE = 0.307; 95% CI 0.153–0.463), TC (SE = 0.217; 95% CI 0.098–0.337), triglyceride (SE = 0.307; 95% CI 0.153–0.463), and hs-CRP (SE = 0.190; 95% CI 0.018–0.362) significantly more than high-intensity statin therapy. In terms of safety, the two treatments were not significantly different in terms of ALT elevation, but high-intensity statin increased AST and CK significantly more than combination therapy. This analysis indicates that low/moderate-intensity statin plus ezetimibe combined therapy is more effective and safer than high-intensity statin monotherapy, which suggests the addition of ezetimibe to statin should be preferred over increasing statin dose and that high-intensity statin should be used more carefully, especially in patients with related risks.

NRP2 promotes atherosclerosis by upregulating PARP1 expression and enhancing low shear stress-induced endothelial cell apoptosis.

Atherosclerosis-related cardiovascular diseases are leading causes of mortality worldwide, characterized by the development of endothelial cell dysfunction, increased oxidized low-density lipoprotein uptake by macrophages, and the ensuing formation of atherosclerotic plaque. Local blood flow patterns cause uneven atherosclerotic lesion distribution, and endothelial dysfunction caused by disturbed flow is an early step in the development of atherosclerosis. The present research aims to elucidate the mechanism underlying the regulation of Neuropilin 2 (NRP2) under low shear stress (LSS) in the atheroprone phenotype of endothelial cells. We observed that NRP2 expression was significantly upregulated in LSS-stimulated human umbilical vein endothelial cells (HUVECs) and in mouse aortic endothelial cells. Knockdown of NRP2 in HUVECs significantly ameliorated cell apoptosis induced by LSS. Conversely, overexpression of NRP2had the opposite effect on HUVEC apoptosis. Animal experiments suggest that NRP2knockdown markedly mitigated the development of atherosclerosis in Apoe-/- mice. Mechanistically, NRP2knockdown and overexpression regulated PARP1 protein expression in the condition of LSS, which in turn affected the expression of apoptosis-related genes. Moreover, the upstream transcription factor GATA2 was found to regulate NRP2 expression in the progression of atherosclerosis. These findings suggest that NRP2 plays an essential proatherosclerotic role through the regulation of cell apoptosis, and the results reveal that NRP2 is a promising therapeutic target for the treatment of atherosclerotic disorders.

Arterial calcification, atherosclerosis and osteoporosis: only clinical associations or a genetic platform?

The review is devoted to the comorbidity of two multifactorial diseases — atherosclerosis and osteoporosis. Numerous epidemiological, experimental and clinical studies have confirmed the relationship between these diseases based on common risk factors and pathogenetic mechanisms. At the same time, to assess the associations between osteoporosis and atherosclerosis-related cardiovascular diseases, the following surrogate markers are used: vascular calcification, vascular stiffness, bone mineral density. It is known that atherosclerosis and osteoporosis depend on the human genotype, and they are caused by the interaction between the environment and genes. The modifiable risk factors for these diseases are largely similar, and the common features of atherosclerosis and osteoporosis pathogenesis make it possible to formulate the concept of a unified genetic basis of their development. Advances in molecular technology have made it possible to conduct a genome-wide association study (GWAS) and successfully identify genetic markers associated with both atherosclerosis and osteoporosis. The review aim was to describe the genes associated with developing atherosclerosis, arterial calcification and osteoporosis, as well as to provide information on the current understanding of the general genetic basis for plaque formation, vascular calcium deposition, and a decrease in bone mass. The analysis of publications from the PubMed, Medline, Web of Science and Cochrane Library databases since 2000 have been carried out. The article describes the genetic markers associated with atherosclerosis and osteoporosis, as well as considers the achievements in studying genetics of osteoporosis and atherosclerosis-related cardiovascular diseases. In addition, modern approaches and directions for further research of these diseases was established. The review can be useful for medical practitioners to clarify various genetic associations and mechanisms that lead to this comorbidity.

DXA Versus Clinical Measures of Adiposity as Predictors of Cardiometabolic Diseases and All-Cause Mortality in Postmenopausal Women

ObjectiveTo investigate whether dual-energy x-ray absorptiometry (DXA) estimates of adiposity improve risk prediction for cardiometabolic diseases over traditional surrogates, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) in older women. Patients and MethodsWe analyzed up to 9744 postmenopausal women aged 50 to 79 years participating in the Women’s Health Initiative who underwent a DXA scan and were free of cardiovascular disease and diabetes at baseline (October 1993 to December 1998) and followed through September 2015. Baseline BMI, WC, WHR, and DXA-derived percent total-body and trunk fat (%TrF) were incorporated into multivariable Cox proportional hazards models to estimate the risk of incident diabetes, atherosclerosis-related cardiovascular diseases (ASCVDs), heart failure, and death. Concordance probability estimates assessed the relative discriminatory value between pairs of adiposity measures. ResultsA total of 1327 diabetes cases, 1266 atherosclerotic cardiovascular disease (ASCVD) cases, 292 heart failure cases, and 1811 deaths from any cause accrued during a median follow-up of up to 17.2 years. The largest hazard ratio observed per 1 standard deviation increase of an adiposity measure was for %TrF and diabetes (1.77; 95% CI, 1.66-1.88) followed by %TrF and broadly defined ASCVD (1.22; 95% CI, 1.15-1.30). These hazard ratios remained significant for both diabetes (1.47; 95% CI, 1.37-1.57) and ASCVD (1.22; 95% CI, 1.14-1.31) even after adjusting for the best traditional surrogate measure of adiposity, WC. Percentage of trunk fat was also the only adiposity measure to demonstrate statistically significant improved concordance probability estimates over BMI, WC, and WHR for diabetes and ASCVD (all P<0.05). ConclusionDXA-derived estimates of abdominal adiposity in postmenopausal women may allow for substantially improved risk prediction of diabetes over standard clinical risk models. Larger DXA studies with complete lipid biomarker profiles and clinical trials are needed before firm conclusions can be made.

Relationship between vascular age and atherosclerosis-related cardiovascular diseases

Aim. To determine the relationship between vascular age (VA) and atherosclerosis-related cardiovascular diseases in patients with hypertension and hyperlipidemia.Material and methods. The study involved 241 residents of Baku. The mean age was 58,7±10,9 years. There were 119 women (49,4%) and 122 (50,6%) men. The mean body mass index was 27,77±4,19 kg/m2. Data on family history, smoking, obesity, diabetes, chronic kidney disease, revascularization, peripheral arterial disease, angina pectoris, drug intake, lipid profile, systolic and diastolic blood pressure were analyzed. Patient VA was estimated using an online calculator.Results. The patient VA was on average 78,0±15,1 years. Pearson's correlation analysis showed a positive correlation between biological age (BA) and estimated VA (0,719; 95% confidence interval: 0,651-0,775; p&lt;0,001). Pearson's chi-squared test with Monte Carlo simulation showed that within 10-month followup, myocardial infarction (MI) in presented sample was more common in age subgroups of 50-59 (10,0%) and 60-69 (8,3%) years. At the same time, in the group defined by VA, myocardial infarction was more common in the age subgroup of 70-79 (7,0%) and &gt;80 years (13,3%). MI+stroke+revascularization in the group defined by BA was more common in age subgroups of 50-59 (12,0%) and 60-69 (14,5%) years, and in the group defined by VA, MI+stroke+revascularization was more common in age subgroups of 70-79 (11,6%) and &gt;80 years (19,9%).Conclusion. A significant positive correlation was found between BA and VA. In case of VA &gt;70 years, the incidence of MI+stroke+revascularization increases approximately 3-5 times. Thus, the assessment of VA is an effective clinical tool that allows to inform the patient about possible cardiovascular events and to develop preventive measures.

Interleukin-36γ aggravates macrophage foam cell formation and atherosclerosis progression in ApoE knockout mice

Atherosclerosis-related cardiovascular diseases are the leading cause of mortality worldwide. Macrophage-derived foam cell formation is a critical early event in atherogenesis. However, the molecular pathways involved in this disease have not been fully elucidated. Interleukin (IL)-36 plays a crucial role in inflammation, and this study was conducted to investigate the possible role of IL-36γ in the pathogenesis and regulation of atherosclerosis. In this study, we show that IL-36γ regulates inflammatory responses and lipoprotein metabolic processes in macrophages and exerts its atherosclerosis-promoting effects by increasing macrophage foam cell formation and uptake of oxidized low-density lipoproteins. Mechanistically, IL-36γ specifically upregulates expression of the scavenger receptor CD36 through the phosphoinositide 3-kinase pathway in macrophages. These results contribute to our understanding of IL-36γ as a novel regulator of foam cell formation and atherogenesis progression.

Identification of miR-17, miR-21, miR-27a, miR-106b and miR-222 as endoplasmic reticulum stress-related potential biomarkers in circulation of patients with atherosclerosis.

Atherosclerosis and related cardiovascular diseases are among the most commoncauses of death worldwide. Unfolded protein response, also known as Endoplasmic reticulum stress, has a critical role in many diseases including atherosclerosis. Small non-coding microRNAs (miRNA), which generally suppress gene expression, regulate UPR signalling and they may also be involved in the progression of atherosclerosis. We aim to investigate the expression levels of miR-17, miR-21, miR-27a, miR-106b, miR-222 and CHOP gene in circulation of atherosclerosis patients compared to healthy controls to establish a link between ERstress and atherosclerosis. miRNAcontaining whole RNAwasisolated from blood samples of25patientswith atherosclerosis and 26healthy controls.Expression levels of miRNAs andCHOP were measured via Real Time PCR method. miR-17and miR-106b were significantly increased whilemiR-21, miR-27a, and miR-222 weresignificantly decreasedin patients compared to controls. CHOP gene wasalso dramaticallyand significantlyinducedin patientsamples. miR-17, miR-21, miR-27a, miR-106b,miR-222and CHOPwere significantly differentially expressed in patients with atherosclerosis. EachmiRNAand CHOPmight regulate atherosclerotic plaque progression andthey canbe used as a biomarker in the diagnosis and follow-up of atherosclerosis-related cardiovascular diseases.

Inflammatory Basis of Atherosclerosis: Modulation by Sex Hormones.

Atherosclerosis-related cardiovascular diseases (CVDs) are the leading cause of death globally. Several lines of evidence are supportive of the contributory role of vascular inflammation in atherosclerosis. Diverse immune cell types, including monocytes/macrophages, T-cells and neutrophils, as well as specialized proresolving lipid mediators, have been successfully characterized as key players in vascular inflammation. The increased prevalence of atherosclerotic CVD in men in comparison to age-matched premenopausal women and the abolition of sex differences in prevalence during menopause strongly suggest a pivotal role of sex hormones in the development of CVD. Indeed, many animal and human studies conclusively implicate sex hormones as a crucial component in driving the immune response. This is further corroborated by the effective identification of sex hormone receptors in vascular endothelial cells, vascular smooth muscle cells and immune cells. Collectively, these findings suggest a cellular communication between sex hormones and vascular or immune cells underlying the vascular inflammation in atherosclerosis. The aim of this review is to provide an overview of vascular inflammation as a causal cue underlying atherosclerotic CVDs within the context of the modulatory effects of sex hormones. Moreover, the cellular and molecular signaling pathways underlying the sex hormones- immune system interactions as potential culprits for vascular inflammation are highlighted with detailed and critical discussion. Finally, the review concludes by speculations on the potential sex-related efficacy of currently available immunotherapies in mitigating vascular inflammation. Conceivably, a deeper understanding of the immunoregulatory influence of sex hormones on vascular inflammation-mediated atherosclerosis permits sex-based management of atherosclerosis-related CVDs.

Familial hypercholesterolemia: current status of the problem, treatment, and prevention

Familial hypercholesterolemia is the most common hereditary disease characterized by an increase in low density lipoprotein cholesterol levels and the premature development of atherosclerosis-related cardiovascular diseases. Diagnosis and treatment of such patients are associated with certain difficulties. This review presents data on the prevalence of familial hypercholesterolemia, identification of patients with such a diagnosis, prevention of adverse cardiovascular events, and also discusses the appointment of lipid-lowering therapy.

Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Do Not Associate with Measures of Sub-Clinical Atherosclerosis: Results from the IMPROVE Study

Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis-related cardiovascular diseases (CVD) share common metabolic pathways. We explored the association between three NAFLD-associated single nucleotide polymorphisms (SNPs) rs738409, rs10401969, and rs1260326 with sub-clinical atherosclerosis estimated by the carotid intima-media thickness (c-IMT) and the inter-adventitia common carotid artery diameter (ICCAD) in patients free from clinically overt NAFLD and CVD. The study population is the IMPROVE, a multicenter European study (n = 3711). C-IMT measures and ICCAD were recorded using a standardized protocol. Linear regression with an additive genetic model was used to test for association of the three SNPs with c-IMT and ICCAD. In secondary analyses, the association of the three SNPs with c-IMT and ICCAD was tested after stratification by alanine aminotransferase levels (ALT). No associations were found between rs738409, rs1260326, rs10401969, and c-IMT or ICCAD. Rs738409-G and rs10401969-C were associated with ALT levels (p < 0.001). In patients with ALT levels above 28 U/L (highest quartile), we observed an association between rs10401969-C and c-IMT measures of c-IMTmax and c-IMTmean-max (p = 0.018 and 0.021, respectively). In conclusion, NAFLD-associated SNPs do not associate with sub-clinical atherosclerosis measures. However, our results suggest a possible mediating function of impaired liver function on atherosclerosis development.

Latent opportunities for the prevention of ischemic stroke in patients with atherosclerosis-related diseases: additional analysis of randomized trials on rivaroxaban

Practical introduction of drugs requires determining the relationship between the benefits of its use and adverse effects, as well as identifying clinically significant additional benefits of new treatment approaches by analyzing additional parameters or reanalyzing data of randomized controlled trials. Despite the lack of evidence of such analyzes, they often affect the prospects of using drugs in a particular clinical situation. The article discusses new data on the prospects for the use of low-dose rivaroxaban (2,5 mg 2 times a day), which were obtained not only in initial analyzes, but also secondary analyzes of data obtained in randomized trials involving patients with atherosclerosis-related cardiovascular diseases and sinus rhythm.

The atheroprotective roles of heart-protecting musk pills against atherosclerosis development in apolipoprotein E-deficient mice.

Heart-protecting musk pill (HMP), derived from Chinese herbal medicines, has been found to possess protective roles against atherosclerosis-related cardiovascular diseases (CVDs), however, the anti-atherosclerotic mechanisms of HMP are still unclear. Here, we investigated the effects of HMP on alleviating atherosclerotic lesion severity in mice and explored the molecular mechanisms. Apolipoprotein E-deficient mice were fed western-type diet supplemented with HMP (25 mg/kg/day) or normal saline gavage for 20 weeks. Then histopathological staining was performed to assess the atheromatous plaque burden. Biochemical kits were used to detect levels of lipid profiles. Moreover, effector factors associated with lipid metabolism in liver and intestinal tissues were investigated by western blot and real-time PCR assays. Levels of signal molecules participating in the mitochondrial-mediated apoptosis pathway were detected by Western blot. We found that HMP notably reduced atherosclerotic lesion size (P<0.05) and improved plaque stability (P<0.05). HMP treatment decreased circulating TC (P<0.01), LDL-C (P<0.01) and TG (P<0.05) levels and increased HDL-C (P<0.05) content. HMP was found to suppress SREBP2, HMGCR and PCSK9 expressions (P<0.05), yet promote LDLR expression (P<0.05) in hepatocytes. Moreover, HMP was discovered to activate PPARα/CPT-1A cascade (P<0.05) and inhibit contents of SREBP1c and the lipogenic genes FAS and ACCα (P<0.05). The LBK1/AMPK cascade was also activated after HMP administration (P<0.05). Additionally, HMP was found to facilitate transintestinal cholesterol excretion by increasing ABCG5 and ABCG8 levels and reducing NPC1L1 content (P<0.05). In terms of vasoprotective activities, we observed that HMP decreased cleaved caspase-3 content (P<0.05) in the vascular intima, which might be due to inhibition of mitochondrial-related signaling pathway. Altogether, our study indicates that HMP plays anti-atherosclerotic roles via regulating lipid metabolism and improving vascular intimal injury.

Changes in Mitochondrial Genome Associated with Predisposition to Atherosclerosis and Related Disease.

Atherosclerosis-related cardiovascular diseases remain the leading cause of morbidity and mortality, and the search for novel diagnostic and therapeutic methods is ongoing. Mitochondrial DNA (mtDNA) mutations associated with atherosclerosis represent one of the less explored aspects of the disease pathogenesis that may bring some interesting opportunities for establishing novel molecular markers and, possibly, new points of therapeutic intervention. Recent studies have identified a number of mtDNA mutations, for which the heteroplasmy level was positively or negatively associated with atherosclerosis, including the disease at its early, subclinical stages. In this review, we summarize the results of these studies, providing a list of human mtDNA mutations potentially involved in atherosclerosis. The molecular mechanisms underlying such involvement remain to be elucidated, although it is likely that some of them may be responsible for the increased oxidative stress, which plays an important role in atherosclerosis.