Process Of Atherosclerosis Research Articles

Risk Factors of Asymptomatic Carotid Artery Disease in Geriatric Evaluated Using Carotid Intima-Media Thickness (IMT) Measurement, the First Indonesian Population Study.

Carotid artery disease in geriatric is one of the important etiologies of stroke, which topped the cause of mortality in Indonesia. Specific prevention should be done as early as asymptomatic disease occurred. Initial assessment can be performed using ultrasound by measuring the intima-media thickness (IMT) of carotid artery, which can evaluate earlier progression of the atherosclerosis process. Unfortunately, we do not have risk factors categorization that show us which geriatric population fall under high-risk stratification to be screened. Study was done to Indonesian geriatric population. Asymptomatic carotid disease was tested positive if IMT was > 0.9 mm without any previous neurological symptoms. Correlation of the result was statistically tested with risk factors of atherosclerotic process, such as sex, body mass index, presence of hypertension, diabetes mellitus, and hypercholesterolemia. Study obtained 104 subjects and showed the prevalence of asymptomatic carotid disease was 37.5%. Two risk factors: diabetes mellitus and hypercholesterolemia were statistically significant ( p = 0.01) with odds ratio (OR) 3.56 (1.31-9.64, 95% confidence interval [CI]) and OR 2.85 (1.25-6.51, CI 95%), respectively. Logistic regression showed the risk was 69.2% by having two of these comorbidities, 47.2 or 42.5% if diabetes mellitus or hypercholesterolemia was present. As diabetes mellitus and hypercholesterolemia were proved to be significant risk factors for asymptomatic carotid artery disease, we recommend performing ultrasound screening to measure carotid artery IMT for geriatric population who had diabetes mellitus and/or hypercholesterolemia for asymptomatic carotid artery disease to be diagnosed and further treated.

Transcatheter aortic valve implantation via transaortic surgical access

We report a case of an 80-years–old patient with a severe, symptomatic aortic valve stenosis and history of ischemic heart disease, previously treated by coronary artery bypass graft surgery. The patient was contraindicated for conventional surgical aortic valve replacement (SAVR) due to advanced age and underlying comorbidity, therefore transcatheter aortic valve implantation (TAVI) has been offered. The access options for the procedure were restricted by the underlying generalized atherosclerosis process causing peripheral vessel disease. We have chosen transaortic access for the patient which in that case was the only possible option. The transaortic valve implantation was successful with satisfactory hemodynamic results, improvement in functional class heart failure of the patient and preserving the function and anatomy of the coronary artery bypass graft. This case report demonstrates that the lack of favorable transfemoral access for TAVI should not be a limitation by itself for the procedure, rather than be stimulus for searching and using new and alternative access for it.

Palmitic acid promotes endothelial-to-mesenchymal transition via activation of the cytosolic DNA-sensing cGAS-STING pathway

Elevated levels of plasma free fatty acids (FFAs) lead to endothelial dysfunction, a process that is involved in the pathogenesis of atherosclerosis. Endothelial-to-mesenchymal transformation (EndMT) has been reported to accelerate endothelial dysfunction during the process of atherosclerosis. However, the underlying mechanisms of EndMT remain poorly understood. The present study aimed to investigate the role of the cytosolic DNA-sensing cyclic GMP-AMP synthase-stimulator interferon gene (cGAS-STING) pathway in palmitic acid (PA)-induced EndMT. Human aortic endothelial cells (HAECs) were exposed to different concentrations of PA, and subsequently its effects on EndMT and the cGAS-STING pathway were assessed. To investigate the role of cGAS-STING pathway on PA-induced EndMT, RNA interference was used to knockdown the expression of cGAS in HAECs prior to their exposure to PA. First, it was observed that PA reduced cell viability and intracellular nitric oxide production, and increased migratory capacity of the HAECs as well as the cellular oxidative stress response, leading to EndMT. Moreover, it was observed that the cGAS-STING pathway was activated in PA-exposed primary HAECs. Activating cGAS-STING pathway via mtDNA directing lead to EndMT in HAECs. Interestingly, cGAS knockdown by RNA interference attenuated PA-induced inflammation, oxidative stress and EndMT in HAECs. Taken together, the results of the present study suggested that the cytosolic DNA-sensing cGAS-STING pathway may have important roles in PA-induced EndMT in endothelial cells.

Small molecule SMU-CX24 targeting toll-like receptor 3 counteracts inflammation: A novel approach to atherosclerosis therapy

Toll-like receptor 3 (TLR3), as an important pattern recognition receptor (PRR), dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases. Atherosclerosis is proved as an inflammatory disease, and inflammatory events involved in the entire process of initiation and deterioration. However, the contribution of TLR3 to atherosclerosis remains unclear. Herein, we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis. Besides, activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules. Conversely, silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation. Given the aberrance in TLR3 functions on atherosclerosis progression, we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy. Therefore, we developed the novel ellipticine derivative SMU-CX24, which specifically inhibited TLR3 (IC50 = 18.87 ± 2.21 nmol/L). In vivo, atherosclerotic burden was alleviated in Western diet fed ApoE−/− mice in response to SMU-CX24 treatment, accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion. Thus, for the first time, we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression, thereby proposing a new strategy and probe for atherosclerosis therapy.

LncRNAs are Involved in the Process of Atherosclerosis at Diverse Levels.

ResumoA aterosclerose é a causa mais comum de doença cardiovascular em todo o mundo, ela está associada a uma alta incidência de eventos clínicos. O acúmulo de evidências elucidou que os RNAs longos não codificantes (LncRNAs) são uma nova classe de transcritos com papéis críticos nos processos fisiopatológicos da aterosclerose. Nesta revisão, resumimos o progresso recente dos LncRNAs no desenvolvimento da aterosclerose. Descrevemos principalmente os diversos mecanismos regulatórios dos LncRNAs nos níveis transcricionais e pós-transcricionais. Este estudo pode fornecer informações úteis sobre os LncRNAs como alvos terapêuticos ou biomarcadores para o tratamento da aterosclerose.

Senescence in Vascular Smooth Muscle Cells and Atherosclerosis.

Vascular smooth muscle cells (VSMCs) are the primary cell type involved in the atherosclerosis process; senescent VSMCs are observed in both aged vessels and atherosclerotic plaques. Factors associated with the atherosclerotic process, including oxidative stress, inflammation, and calcium-regulating factors, are closely linked to senescence in VSMCs. A number of experimental studies using traditional cellular aging markers have suggested that anti-aging biochemical agents could be used to treat atherosclerosis. However, doubt has recently been cast on such potential due to the increasingly apparent complexity of VSMCs status and an incomplete understanding of the role that these cells play in the atherosclerosis process, as well as a lack of specific or spectrum-limited cellular aging markers. The utility of anti-aging drugs in atherosclerosis treatment should be reevaluated. Promotion of a healthy lifestyle, exploring in depth the characteristics of each cell type associated with atherosclerosis, including VSMCs, and development of targeted drug delivery systems will ensure efficacy whilst evaluation of the safety and tolerability of drug use should be key aims of future anti-atherosclerosis research. This review summarizes the characteristics of VSMC senescence during the atherosclerosis process, the factors regulating this process, as well as an overview of progress toward the development and application of anti-aging drugs.

Pinolenic acid exhibits anti-inflammatory and anti-atherogenic effects in peripheral blood-derived monocytes from patients with rheumatoid arthritis

Pinolenic acid (PNLA), an omega-6 polyunsaturated fatty acid from pine nuts, has anti-inflammatory and anti-atherogenic effects. We aimed to investigate the direct anti-inflammatory effect and anti-atherogenic effects of PNLA on activated purified CD14 monocytes from peripheral blood of patients with rheumatoid arthritis (RA) in vitro. Flow cytometry was used to assess the proportions of CD14 monocytes expressing TNF-α, IL-6, IL-1β, and IL-8 in purified monocytes from patients with RA after lipopolysaccharide (LPS) stimulation with/without PNLA pre-treatment. The whole genomic transcriptome (WGT) profile of PNLA-treated, and LPS-activated monocytes from patients with active RA was investigated by RNA-sequencing. PNLA reduced percentage of monocytes expressing cytokines: TNF-α by 23% (p = 0.048), IL-6 by 25% (p = 0.011), IL-1β by 23% (p = 0.050), IL-8 by 20% (p = 0.066). Pathway analysis identified upstream activation of peroxisome proliferator-activated receptors (PPARs), sirtuin3, and let7 miRNA, and KLF15, which are anti-inflammatory and antioxidative. In contrast, DAP3, LIF and STAT3, which are involved in TNF-α, and IL-6 signal transduction, were inhibited. Canonical Pathway analysis showed that PNLA inhibited oxidative phosphorylation (p = 9.14E−09) and mitochondrial dysfunction (p = 4.18E−08), while the sirtuin (SIRTs) signalling pathway was activated (p = 8.89E−06) which interfere with the pathophysiological process of atherosclerosis. Many miRNAs were modulated by PNLA suggesting potential post-transcriptional regulation of metabolic and immune response that has not been described previously. Multiple miRNAs target pyruvate dehydrogenase kinase-4 (PDK4), single-immunoglobulin interleukin-1 receptor molecule (SIGIRR), mitochondrially encoded ATP synthase membrane subunit 6 (MT-ATP6) and acetyl-CoA acyltranferase2 (ACAA2); genes implicated in regulation of lipid and cell metabolism, inflammation, and mitochondrial dysfunction. PNLA has potential anti-atherogenic and immune-metabolic effects on monocytes that are pathogenic in RA and atherosclerosis. Dietary PNLA supplementation regulates key miRNAs that are involved in metabolic, mitochondrial, and inflammatory pathways.

C82 PROCEDURES AND DEVICES FOR CALCIUM TREATMENT IN AN INCREASINGLY COMMON SCENARIO: YOUNG ONCOLOGIC PATIENTS

Abstract Background Cardiovascular disease and cancer have a high prevalence in Western countries, sharing many risk factors: obesity, diabetes, cigarette smoking, advanced age, diet and sedentary lifestyle. There is growing evidence that patients with ischemic heart disease (CAD) have a higher risk of developing cancer and, conversely, patients with a history of cancer are exposed to a higher incidence of CAD. In particular, cancer and its related therapies may promote the process of atherosclerosis, often with high calcific burden. Case Report This is a case of a 58 years old gentleman with a past smoking habit. Unfortunately from 2019 he was diagnosed by a stage IV lung adenocarcinoma, actually in 3rd line therapy: Carboplatin–Alimta, Atezolizumab and Paclitaxel weekly; no metastatic localizations was found at follow up CT scan. Last July, the patient complained of breath fatigue during exertion. At a complete cardiologic examination EKG was normal, and severe aortic stenosis was detected with concentric left ventricular hypertrophy, preserved ejection fraction. At CT scan, the aortic valve was confirmed as bicuspid Sievers type 0 (Figure 1, panel A). Vmax was 5.49 cm/s, max gradient was up to 120 mmHg, and medium gradient was 67 mmHg, as shown in Figure 1, panel B. Coronary angiography showed a very severe, focal, concentric calcific lesion of the left anterior descendant branch (Figure 2, Panel A). The patient was then referred to our local Heart Team and due to his oncological condition with prognosis >12 months, we decided to treat him percoutaneously. Aortic stenosis was treated Transcatheter Aortic Valve Implantation (TAVI) a few days later: predilatation, implant of a with a balloon–expandable valve Edwards Sapien 3 n°23 and post–dilatation, by femoral access (Figure 2, four steps of TAVI). Coronary lesion was uncrossable with the lowest profile balloons, so rotatripsy was perfomed: rotational atherectomy followed by 40 pulses of lithotripsy with Shockwave (Figure 2, Panel B and C). Everolimus eluting stent 3.00 x 23 mm was implanted and optimized (Figure 2, Panel D). Conclusion Recent devices and techniques in Invasive Cardiology allow percutaneous therapies for patients with time–dependent diseases, such as patients with advanced lung adenocarcinoma. Lately, oncological therapies for this type of lung cancer are very promising, allowing the combination of interventional procedures capable of further increasing the prognosis of these patients.

Carotid Plaque Composition and the Importance of Non-Invasive in Imaging Stroke Prevention.

Luminal stenosis has been the standard feature for the current management strategies in patients with atherosclerotic carotid disease. Histological and imaging studies show considerable differences between plaques with identical degrees of stenosis. They indicate that specific plaque characteristics like Intraplaque hemorrhage, Lipid Rich Necrotic Core, Plaque Inflammation, Thickness and Ulceration are responsible for the increased risk of ischemic events. Intraplaque hemorrhage is defined by the accumulation of blood components within the plaque, Lipid Rich Necrotic Core is composed of macrophages loaded with lipid, Plaque Inflammation is defined as the process of atherosclerosis itself and Plaque thickness and Ulceration are defined as morphological features. Advances in imaging methods like Magnetic Resonance Imaging, Ultrasound, Computed Tomography and Positron Emission Tomography have enabled a more detailed characterization of the plaque, and its vulnerability is linked to these characteristics, changing the management of these patients based only on the degree of plaque stenosis. Studies like Rotterdam, ARIC, PARISK, CAPIAS and BIOVASC were essential to evaluate and prove the relevance of these characteristics with cerebrovascular symptoms. A better approach for the prevention of stroke is needed. This review summarizes the more frequent carotid plaque features and the available validation from recent studies with the latest evidence.

ПАТОФИЗИОЛОГИЧЕСКАЯ РОЛЬ ОСТЕОПРОТЕГЕРИНА ПРИ АТЕРОСКЛЕРОЗЕ И САХАРНОМ ДИАБЕТЕ

Diabetes mellitus is rightly called non-infectious epidemic of the 21st century. At the same time, cardiovascular diseases still remain the leading cause of death in the world. A combination of diabetes mellitus and peripheral arterial disease increases the risk of the lower limb loss and death many times over. There are many concepts concerning the mechanism of development of these diseases. In recent years, there is more and more data evidencing the similarity of the processes of atherosclerosis and osteoporosis development. The connecting link between these processes may be osteoprotegerin (OPG). Information has been obtained on osteoprotegerin as an antiresorptive factor participating in the RANKL-RANK-OPG system. Under pathophysiological conditions, OPG is expressed in the vascular wall, including being found at different stages of atherosclerotic plaque formation. The RANKL-RANK-OPG signaling pathway is involved in the process of bone tissue remodeling. The mechanisms of atherosclerosis and osteoporosis development are similar; nevertheless, they require further study.

Relationship of 5-year changes in inflammatory, metabolic and oxidative biomarkers with cardiovascular diseases incidence at 10-years

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Carlos III Health Institute and the European Regional Development Fund Government of Catalonia through the Agency for Management of University and Research Grants Background Early stratification of cardiovascular (CV) risk saves thousands of lives every year. There is a debate about the value of determining genetic or plasma biochemical biomarkers, related to atherosclerosis process, to improve the prediction of an incident CV disease. While, single measurements of some of these biomarkers have been associated with an increased risk of CV disease, the change of the levels of these biomarkers over time could also improve the prediction of CV events and drive the identification of new biological pathways and therapeutic targets. Purpose This study aimed to examine the relationship between 5-year change in the levels of biomarkers of inflammation (TNF-α, IL-10, IL-6, MCP-1, and CRP), glucidic metabolism (adiponectin, leptin, and insulin) and oxidation (GHS-Px), and the incidence of CV events at 10 years in a population without previous CV disease. Methods This was a cohort study nested in a large population cohort. Participants were randomly selected from the REGICOR cohort (North-Eastern Spain) recruited in 2005 (6.352 participants). Biomarkers were measured at baseline and in a re-examination in 2010. Participants were followed until 2020 for a composite CV disease endpoint including fatal and non-fatal first occurrence of coronary artery disease, stroke and peripheral artery disease. Baseline characteristics were compared between participants with and without CV events with standard parametric and non-parametric methods, as required. We used Cox regression to analyse the effect of the 5-year change of the biomarker levels on the occurrence of the composite endpoint adjusted for age, sex, baseline levels of each biomarker and classical CV risk factors. Results We included 419 individuals aged 35 to 74 years. Overall, 6.2% developed an incident CV disease within the 10-year follow-up. Characteristics of participants, who had or not a CV event, are compared in Table 1. Cases had a more adverse CV and anthropometric risk profile. Compared to individuals with sustained IL-6 and insulin levels, those with increased IL-6 or insulin after five years were at higher independent risk of CV disease at ten years. After adjusting for potential confounders, an increased IL-6 and insulin at the 5-year follow-up were independently associated with CV disease at 10-years (Table 2). Each rise of IL-6 or insulin in 1pg/mL or 10pg/mL, respectively, increased 32% (IL-6) and 2% (insulin) the risk of developing a CV event at 10-years. Conclusions Increasing IL-6 and insulin levels over five years indicates a higher risk of CV disease ten years thereafter, independently of classical risk factors.

Pyroptosis-Related Gene Signature and Expression Patterns in the Deterioration of Atherosclerosis.

Background Pyroptosis has been shown to be involved in the overall process of atherosclerosis. This study was aimed at investigating pyroptosis-related gene expression patterns in atherosclerosis and their diagnostic significance. Methods and Results In GSE100927, fifty-four pyroptosis-related genes were identified. Between atherosclerotic plaques and normal samples, the expression patterns of pyroptosis-related genes were significantly different. In order to construct a pyroptosis-related risk score signature (PRSS), the least absolute shrinkage and selection operator (LASSO) was combined with multivariate logistic regression to screen twelve genes. The diagnostic efficiency of the PRSS performed well in GSE43292, as shown by the results of receiver-operating characteristics (ROCs). Consensus clustering identified two expression patterns of pyroptosis-related genes in different statuses of atherosclerotic plaque in GSE163154. The biological behavior of the different clusters was examined by the gene set variation analysis (GSVA). The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses revealed that the differentially expressed genes (DEGs) in the two clusters were enriched in the immune response. The Cytoscape software was used to construct protein-protein interaction (PPI) networks for hub gene screening. Following that, the Drug Gene Interaction Database (DGIdb) was utilized to find 47 possible medicines and chemical compounds that interact with hub genes in atherosclerotic plaques. Conclusion The results of this study showed that pyroptosis-related genes contribute to the progression of atherosclerosis and may serve as biomarkers in clinical diagnosis as well as novel therapeutic targets for the treatment of AS.

MO732: Circulating Omentin-1 and Subclinical Atherosclerosis in Chronic Haemodialysis Patients: A Pilot Study

Abstract BACKGROUND AND AIMS Chronic haemodialysis (HD) patients are notoriously at high risk for cardiovascular mortality and morbidity. Omentin-1 (OME-1) is an adipocytokine produced by adipose tissue, whose levels are altered in various dysmetabolic conditions, such as obesity and type 2 diabetes mellitus. Beyond this, nowadays there is evidence indicating that this cytokine plays a crucial role in the genesis and progression of systemic atherosclerosis since it may inhibit plaque formation. With this background in mind, we run a pilot investigation to evaluate the possible correlation between circulating OME-1 levels and mean intimal thickness (IMT) in a small, homogeneous cohort of patients treated by HD (‘HD patients’). METHOD From a source cohort of 45 HD patients, we selected 27 individuals suitable to be enrolled. These patients had a dialysis vintage > 6 mo., were on a regular 4 h/3 times week HD regimen and had stable clinical conditions. OME-1 levels were measured in their blood by the ELISA together with common laboratory and clinical parameters before starting a mid-week HD session. All the patients then underwent carotid Doppler ultrasound for IMT measurement. A total of 18 healthy subjects were the controls. RESULTS In the whole cohort, mean IMT values were 0.75 ± 0.12 mm. However, 8/27 patients (29.6%) presented a pathological IMT (>1 mm). Circulating OME-1 levels in the whole HD cohort were increased as compared with controls [763 (367–1423) versus 371 (228–868) ng/mL; P = 0.03]. However, HD patients with pathological IMT presented, on average, lower OME-1 levels as compared with others [483.25 (168.7–1743) versus 1155 (286–2324); P = 0.05]. In ROC analyses, OME-1 values ≤ 840 ng/mL held an 83.3 sensitivity and 66.7 specificity (AUC 0.716, 95% confidence interval 0.506–0.946) in identifying HD patients with pathological carotid thickening. CONCLUSION OME-1 may play a direct role in the atherosclerosis process also in HD patients. Further studies on larger and more heterogeneous HD cohorts are needed to confirm the usefulness of OME-1 plasma levels as potential biomarkers for diagnosing subclinical atherosclerosis and for stratifying the risk of atherosclerosis progression in high-CV risk in HD patients.

Abstract 105: Proprotein Convertase Subtilisin/kexin Type 6 (Pcsk6) Plays A Role In Angiogenesis Regulation

Background: PCSK6 cleaves and activates growth factors involved in cell differentiation and Pcsk6-/- mice exhibit 25% embryonic lethality, while surviving offspring have blindness and cyclopia. We have shown that PCSK6 localizes to vascular smooth muscle cells of intra-plaque neovessels. We therefore hypothesize that the processes of angiogenesis, atherosclerosis and plaque neovascularisation share common molecular regulators and that PCSK6 plays a role in these processes. Methods: Association between SNPs near the PCSK6 gene and levels of 90 plasma proteins was tested using data from 30,931 individuals in the SCALLOP consortium. Associations of angiogenic factors with PCSK6 (transcriptomic and proteomic) and patient symptomatology were explored in a biobank of plaque endarterectomies (BiKE). Morpholino technology was used for Pcsk6 knockdown in zebrafish, coupled with vascular phenotype studies. Pcsk6-/- mice were used to study the expression of vasculogenesis related genes and vascular morphology at baseline (12 weeks). Results: Rs7178801 and rs11639051 in the PCSK6 gene were found to relate to plasma PDGFB and VEGFD levels. TGFB2, VEGFA, VEGFC, PDGFA and PLAUR associated with patients symptomatology in BiKE and correlated with PCSK6 levels. Gross phenotypic and histological examination of zebrafish embryos with ablated PCSK6 showed improper peripheral vascular patterning of intersegmental vessels along with cerebral and myocardial haemorrhage hemorrhage. Expression of angiogenic factors; Vegfa, Vegfb, Angpt1 and Tgfb2 were altered in the heart, liver and adipose tissue in Pcsk6-/- mice. Vessel density, length and branch numbers were reduced in the Pcsk6 -/- compared to the controls in the superficial but more significantly in the deep peripheral vessels. The smooth muscle cell coverage of the retinal vasculature was also reduced in the Pcsk6 -/- mice vs controls and Pdgfa was significantly downregulated compared to controls in mouse retinas. Conclusions: PCSK6 associates with levels of angiogenic factors on the genetic, transcriptomic and proteomic level. Lack of Pcsk6 in mice and zebrafish led to vascular patterning defects. Further planned studies will examine PCSK6 in pathological neovascularization.

The association of Helicobacter Pylori infection with dyslipidaemia and other atherogenic factors in dyspeptic patients at St. Paul's Hospital Millennium Medical College

BackgroundStudies showed that more than half of Ethiopians were presumed to be chronically infected with H. pylori. Nowadays, evidence has come to the literature strongly suggesting the potential association between H. pylori and extra gastric disorders including atherosclerosis. ObjectiveTo assess the association of helicobacter pylori infection with dyslipidaemia and other atherogenic factors in dyspeptic patients at St. Paul's Hospital Millennium Medical College, from November 2019 to June 2020. Materials and methodsThis institution-based cross-sectional study was examining 346 dyspeptic patients at SPHMMC from November 2019 to June 2020. A structured questionnaire was used to collect socio-demography data and anthropometric measurement was taken. Biochemical parameters were measured in serum samples by using Cobas 6000 clinical chemistry analyzer. Data were coded and entered into a statistical package for social sciences (SPSS) version 23 for analysis. Risk factors were identified using logistic regression. Hence, a bivariate logistic regression analysis test was conducted and variables with a p < 0.25 were included in the multivariate logistic regression model. P-values ≤0.05 were considered as a cut point for statistical significance in the final model. ResultsAn overall prevalence of dyslipidemia among study participants was 253 (73.12 %). Among those who tested positive for H. pylori, 119/174 (68.39 %) had dyslipidemia in at least one lipid profile, while 8 (4.60%) had dyslipidemia in all four lipid profiles. After adjusting for traditional dyslipidemia risk factors, age >45 (AOR 4.864, 95% CI 2.281–4.080, P < 0.001), systolic blood pressure >120mmHg (AOR 1.036, 95% CI 1.009–1.065, P = 0.036) and being H. Pylori seropositive (AOR 0.555, 95% CI 0.318–0.967, P = 0.038) were an independent predictors of dyslipidemia. ConclusionThis study reported that more than two-thirds of the H. pylori seropositive groups had exhibited dyslipidemia in at least one lipid profile, which can accelerate the incidence of atherosclerosis process.

Correlation between predominantly subclinical peripheral arterial disease in patients with ischemic stroke: A study using ankle–brachial index from rural eastern India

Introduction: Peripheral arterial disease (PAD) decreases arterial perfusion leading to limb ischemia. It is considered one of the markers of subclinical atherosclerosis process. For this reason, it can be a major risk factor for ischemic stroke. Early detection of PAD has an important role in preventing ischemic stroke. Materials and Methods: This study was carried out in District Hospital, Barasat, Kolkata, from March 2011 to March 2013. Eighty-two patients with ischemic stroke (aged 40–80 years) were recruited. Patients having atrial fibrillation and diabetes mellitus and embolic source were excluded. Ankle–brachial index (ABI) was performed with ultrasonography Doppler in each patient. PAD was diagnosed when the ABI was below 0.9. The severity of stroke was assessed by the National Institutes of Health Stroke Scale. Statistical Analysis: For continuous variables, analysis of variance was used to compare three or more groups of patients and Student’s t-test for two groups. Chi-square test or Fisher’s exact test was used for categorical variables. For all analytical purposes, a two-tailed P &lt; 0.05 was considered statistically significant. Results: According to ABI, 62 patients had no pad, 13 patients had mild, and 7 patients had severe PAD. High total cholesterol and low-density lipoprotein were significantly associated with low ABI (P = 0.001). High total cholesterol levels and low ABI were significantly correlated (P &lt; 0.001). A significant association between moderately-low ABI and recurrent stroke was noted (P = 0.019). Conclusion: PAD is significantly associated with recurrent ischemic strokes. Evaluation of ABI for PAD revealed increased risk of recurrent stroke.

Systemic Inflammation, Oxidative Stress and Cardiovascular Health in Children and Adolescents: A Systematic Review.

Recent studies indicate that cerebrovascular diseases and processes of atherosclerosis originate in the childhood era and are largely influenced by chronic inflammation. Some features of vascular dysfunction in adulthood may even be programmed prenatally via genetic influences and an unfavorable intrauterine milieu. Oxidative stress, defined by an imbalance between the production and generation of reactive oxygen species (ROS) in cells and tissues and the capability of an organism to scavenge these molecules via antioxidant mechanisms, has been linked to adverse cardiovascular health in adults, yet has not been systematically reviewed in the pediatric population. We performed a systematic search as per the PRISMA guidelines in PubMed/Medline and Cochrane Reviews and detected, in total, 1228 potentially eligible pediatric articles on systemic inflammation, oxidative stress, antioxidant use, cardiovascular disease and endothelial dysfunction. The abstracts and full-text manuscripts of these were screened for inclusion and exclusion criteria, and a total of 160 articles were included. The results indicate that systemic inflammation and oxidative stress influence cardiovascular health in many chronic pediatric conditions, including hypertension, obesity, diabetes mellitus types 1 and 2, chronic kidney disease, hyperlipidemia and obstructive sleep apnea. Exercise and diet may diminish ROS formation and enhance the total serum antioxidant capacity. Antioxidant supplementation may, in selected conditions, contribute to the diminution of the oxidative state and improve endothelial function; yet, in many areas, studies provide unsatisfactory results.

RGC-32′ dual role in smooth muscle cells and atherogenesis

Proliferation of endothelial cells (EC) and smooth muscle cells (SMC) is a critical process in atherosclerosis. Here, we investigated the involvement of sublytic C5b-9 effector Response Gene to Complement 32 (RGC-32) in cell cycle activation, phenotypic switch, and production of extracellular matrix (ECM) in SMC. Overexpression of RGC-32 augmented C5b-9-induced cell cycle activation and proliferation of SMC in an ERK1-dependent manner and silencing of RGC-32 inhibited C5b-9-induced cell cycle activation. C5b-9-induced cell cycle activation also required phosphorylation of RGC-32 at threonine 91. We found that ECM components fibronectin and collagens I-V were expressed by SMC in human aortic atherosclerotic tissue. Silencing of RGC-32 in cultured SMC was followed by a significant reduction in TGF-β-induced expression of SMC differentiation markers myocardin, SM22 and α-SMA, and that of collagens I, IV and V. These data suggest that RGC-32 participates in both sublytic C5b-9-induced cell cycle activation and TGF-β-induced ECM production.

YY1 affects the levels and function of fibulin-5 in ox-LDL-treated vascular smooth muscle cells.

Fibulin-5 is reportedly involved in the pathological process of atherosclerosis (AS) where low expression has been frequently observed in ruptured atherosclerotic plaques. The aim of the present study was to determine the effects of fibulin-5 on the responses of vascular smooth muscle cells (VSMC) to oxidized low-density lipoprotein (ox-LDL). The expression of fibulin-5 was studied in human aortic-VSMCs (HA-VSMCs) treated with ox-LDL. Fibulin-5 was first overexpressed by the transfection of Ov-Fibulin-5 plasmids in HA-VSMCs challenged with ox-LDL to investigate its influence on cell proliferation, migration and invasion using Cell Counting Kit-8, wound healing and Transwell assays. Yin Yang-1 (YY1) was bioinformatically predicted to bind to the promoter sites of fibulin-5, which was subsequently confirmed by dual-luciferase reporter gene assay. Fibulin-5 overexpression was able to suppress cell proliferation, invasion and migration, which was effectively reversed by YY1 silencing by the transfection of siRNA-Fibulin-5 plasmids which could induced fibulin-5 silencing. YY1 binding sites in the promoter region of fibulin-5 were identified and confirmed in vitro by chromatin immunoprecipitation assay and dual-luciferase reporter gene assay. The present results suggested that as a modulator of fibulin-5, YY1 alleviated ox-LDL-induced proliferation, invasion, migration and phenotypic transition from differentiated contractile phenotype to dedifferentiated phenotype in VSMCs. However, the mechanism underlying the YY1-mediated regulation of fibulin-5 expression needs to be confirmed further in vivo. Nevertheless, targeting fibulin-5 and YY1 could be further developed for AS therapy.

A functional DNA nanosensor for highly sensitive and selective imaging of ClO− in atherosclerotic plaques

Atherosclerosis (AS) is the primary cause of cardiovascular disorders, which lead to one-third of all death globally. However, the atherosclerosis process remains elusive due to the lack of appropriate analytical methods. Herein, we present the first nanoflare-based DNA sensor that could report the distribution of ClO− (a typical marker of AS) in the atherosclerotic plaques. ClO−-responsive phosphorothioate (PS) was inserted into DNA, which was then assembled with a gold nanoparticle (AuNP) core to form a ClO−-specific nanoflare probe. The hydrolysis between PS and ClO− triggered fluorescence turn-on of the probes, showing excellent sensitivity (as low as 8.51 nM) and specificity for ClO− detection. In addition, the nanoflare probes exhibit superior performance in tracing the variations of endogenous and exogenous ClO− in living RAW264.7 cells. After intravenous injection, the efficient accumulation of probes and fluorescence signal enhancement were observed in the atherosclerotic plaques of AS model mice. The nanoflare probes possess significant feasibility in the precise identification of atherosclerotic plaques, which holds tremendous implications for clinical diagnosis, mechanism study, and assessment of therapeutic outcomes associated with AS.