Role In Formation Of Atherosclerosis Research Articles

Differences Between Patients with and without Atherosclerosis in Expression Levels of Inflammatory Mediators in the Adipose Tissue Around the Coronary Artery

Perivascular adipose tissue (PVAT) secretes large amounts of inflammatory mediators and plays a certain role in atherosclerosis formation from the exterior of the vessel. In the present study, we examined the expression level of inflammation-related mediators using adipose tissue samples harvested from patients with and without coronary artery disease (CAD). The subjects were 23 patients who underwent elective coronary bypass surgery (CAD group) and 17 patients who underwent elective mitral valve surgery (non-CAD group) between January 2017 and March 2018. The adipose tissue was harvested from three sites: the ascending aorta (AO), subcutaneous fat (SC), and pericoronary artery (CO) for the measurement of the expression levels of interleukin (IL) -1β, IL-6, IL-10, tumor necrosis factor (TNF) -α, interferon (INF) -γ, and arginase (Arg) -1. In both the non-CAD and CAD groups, the expression levels of all mediators, except Agr-1, which showed a tendency to have higher levels in the SC than in the AO and CO, tended to upregulate in the AO than in the SC and CO. The CAD group had higher values of almost all mediators, except Arg-1. Most importantly, the expression levels of IL-1β, IL-6, and IL-10 in the coronary artery were significantly higher in the CAD group. The expression levels of inflammatory mediators in the pericoronary adipose tissue were significantly higher in the CAD than in the non-CAD group. The adipose tissue appears to influence atherosclerosis formation from the exterior of the coronary artery.

Association of blood lipids, cortisol and Hemodynamics Under stress: A possible role in early Atherogenesis

Introduction: High blood cholesterol is claimed as a risk factor but recently it is accepted that cholesterol is increased under psychological stress. When raised in blood, cholesterol plays role in atherosclerosis formation; a role which is being debated since last many decades but still various questions is un-answered. Role of stress in early atherogenesis with association to alteration in blood lipids has been proposed but the available literature is scanty on the subject.
 Objective: To explore the association of alterations in blood lipids, cortisol level and hemodynamics under mental stress in youth with no apparent heart disease.
 Methodology: 114 male participants were selected from 397 volunteers as per ‘selection criterion’ approved by scientific committee. The volunteers were examined two times: during stress task as ‘stress-study’ and during non-stress period as ‘control’ according to ‘paired sample’ design. Thus, 56.54% apparently healthy subjects were included with exclusion ratio of 43.58%. All experiments were conducted under standard methods at LINAR-Larkana and Physiology Department of Sindh University, Jamshoro. Blood sample were taken between 9.00 am to 12.00 pm.
 Results: Cortisol, systolic and diastolic blood pressures and heart rate were significantly increased during stress session. Different lipid levels were changed with different significant values. Correlations of some altered lipid levels with raised values of hemodynamics and cortisol detected were positive and significant.
 Conclusion: Most changes in the level of variables were found prone to be “atherogenic in pattern” due to psychological stress. This work may pave a way for better understanding of relationship in between lipid alterations, mental stress and early atherogenesis. For that further studies are needed.
 
 Key Words: Cholesterol, Hemodynamics, Cortisol, psychological stress.

Serum CXCL10 and CXCL12 chemokine levels are associated with the severity of coronary artery disease and coronary artery occlusion

BackgroundCardiovascular disease constitutes a major cause of death worldwide. Inflammation plays an important role in atherosclerosis formation, coronary artery disease progression, acute coronary thrombosis and occlusion. Chemokines are inflammatory mediators disposing several bio-functions, as leukocyte migration towards inflammatory signals and vascular injuries. The present study was designed to evaluate the potential correlation between serum levels of chemokines CXCL-10 and CXCL-12 and the degree of coronary artery occlusion. MethodsEighty eight patient candidates for coronary angiography with coronary artery disease symptoms and potentially high risk of coronary artery occlusion were recruited. Chemokine serum levels were measured with the ELISA method and patients underwent coronary angiography. All patients with coronary artery disease (CAD) were divided into four groups according to the Gensini score. Data were presented as mean±SD. All P values <0.05 were considered significant. ResultsOur demographic data showed that of the 88 patients, 46 were male and 42 female. The mean age of patients was 57.95±11.13. Following increased coronary artery occlusion the serum levels of chemokines were significantly increased (CXCL-10 and CXCL-12; P<0.0001 and P<0.0001, respectively). ConclusionIn this novel study, a significant correlation between the serum levels of CXCL-10 and CXCL-12 and the severity of coronary artery occlusion was found. This could be attributed to the role of these chemokines in the processes of angiogenesis and angiostasis, a biological phenomenon that can play key role in the development of collateral circulation.

Hyperhomocysteinemia-Induced Monocyte Chemoattractant Protein-1 Promoter DNA Methylation by Nuclear Factor-κB/DNA Methyltransferase 1 in Apolipoprotein E–Deficient Mice

Hyperhomocysteinemia is considered to be a significant risk factor in atherosclerosis and plays an important role in it. The purpose of this study was to determine the molecular mechanism of blood monocyte chemoattractant protein-1 (MCP-1) promoter DNA hypomethylation in the formation of atherosclerosis induced by hyperhomocysteinemia, and to explore the effect of nuclear factor-κB (NF-κB)/DNA methyltransferase 1 (DNMT1) in this mechanism. The atherosclerotic effect of MCP-1 in apolipoprotein E–deficient (ApoE−/−) and wild-type C57BL/6J mice was evaluated using atherosclerotic lesion area; serum NF-κB, MCP-1, and DNMT1 levels; and MCP-1 promoter DNA methylation expression. In vitro, the mechanism responsible for the effect of NF-κB/DNMT1 on foam cells was investigated by measuring NF-κB and DNMT1 levels to determine whether NF-κB/DNMT1 had an effect on gene expression. Compared with the control group, atherosclerotic lesions in ApoE−/− mice fed a high methionine diet significantly increased, as did the expression of MCP-1. In vitro study showed that pyrrolidine dithiocarbamate treatment down-regulated levels of NF-κB and raised DNMT1 concentrations, confirming the effect of NF-κB/DNMT1 in the MCP-1 promoter DNA methylation process. In conclusion, our results suggest that through NF-κB/DNMT1, MCP-1 promoter DNA hypomethylation may play a key role in formation of atherosclerosis under hyperhomocysteinemia.

Association of inflammatory response gene polymorphism with atherothrombotic stroke in Northern Han Chinese

Atherosclerosis is an important pathophysiological basis of atherothrombotic stroke (ATS), and inflammation plays a significant role in atherosclerosis formation. In this study, single-nucleotide polymorphisms (SNPs) in three key inflammation-related genes, 5-lipoxygenase activating protein (ALOX5AP), phosphodiesterase 4D (PDE4D), and interleukin-1α (IL-1α), were investigated to determine their association with ATS in Northern Han Chinese. Six-hundred and eighty-two ATS patients and 598 unrelated controls were recruited. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and matrix-assisted laser desorption ionization time-of-flight mass spectrometry primer extension. The genotype and allele frequencies of each SNP were statistically analyzed. Risk of ATS was found for the ALOX5AP SG13S114A/T AA genotype (P = 0.040) and A allele (P = 0.033), PDE4D SNP83C/T TT genotype (P = 0.010) and T allele (P = 0.008) and SNP219A/G GG genotype (P = 0.025) and G allele (P = 0.022), and the IL-1α-889C/T T allele (P = 0.035). The differences still remained significant after adjustment. The ALOX5AP HapA haplotype was not correlated with ATS (P = 0.834), but GCGA represented an at-risk haplotype (P = 0.008). Furthermore, the PDE4D AA haplotype at SNP219-220 might be an at-risk haplotype (P = 0.013), while GA might be a protective haplotype (P = 0.005). The ALOX5AP (SG13S114A/T), PDE4D (SNP83C/T, 219A/G), and IL-1α (-889C/T) SNPs were associated with an increased risk of ATS in Northern Han Chinese.

Effects of Panax notoginseng saponins on proliferation and apoptosis of vascular smooth muscle cells

Atherosclerosis is a common cardiovascular disease, and linked with the development of many cardiovascular complications, such as myocardial ischemia and stroke. Although pathogenesis of atherosclerosis is not completely elucidated, increasing evidence has demonstrated that abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in formation of atherosclerosis. Previous studies showed that saponins from Panax notoginseng (PNS) possess anti-atherosclerotic properties. However, the mechanism of PNS against atherosclerosis is not well understood. Therefore, the present study observed the effects of PNS on proliferation and apoptosis of VSMCs. Rat VSMCs were cultured, and platelet-derived growth factor (PDGF) was used to stimulate cell proliferation. The viability of VSMCs was assessed with the MTT method. VSMCs apoptosis was detected by flow cytometry. Expressions of apoptosis related protein p53, Bax, caspase-3 and Bcl-2 were determined using Western blot. Pretreatment of the cells with PNS (200, 400, 800 μg/mL) significantly inhibited proliferation of PDGF-stimulated VSMCs, and induced apoptosis of the proliferated VSMCs in a concentration-dependent way. Western blot analysis showed that PNS upregulated expressions of pro-apoptotic protein p53, Bax and caspase-3, downregulated expression of anti-apoptotic protein Bcl-2, and enlarged Bax/Bcl-2 ratio in the proliferated VSMCs induced by PDGF. This study demonstrates that PNS both inhibits VSMCs proliferation and induces VSMCs apoptosis through upregulating p53, Bax, caspase-3 expressions and downregulating Bcl-2 expression, which constitute the pharmacological basis of its anti-atherosclerotic action.

Dynamic curvature strongly affects wall shear rates in a coronary artery bifurcation model

This study was motivated by the need for a better understanding of coronary artery blood flow patterns and their possible role in atherosclerosis formation. Of particular interest in this study was the effects of the dynamic deformation due to myocardial contraction on wall shear rate patterns in the coronary arteries. A better understanding of these effects on wall shear rate in a bifurcation geometry and an evaluation of the importance of these effects was desired. A three-dimensional computer model of a bifurcation lying on the surface of a sphere with time-varying radius of curvature was employed to simulate the motion and deformation of the arteries. The results indicated low mean shear rates along the myocardial wall and very high shear rate variations (over 100% of the static mean shear rate) along the outer wall. The results obtained using a quasi-static analysis were found to underestimate the dynamic wall shear rate variation along the myocardial and outer walls. It was concluded that dynamic geometry effects are important in determining sites of low mean and oscillating wall shear that have been associated with atherogenesis in curved, bifurcating arteries.