Abstract

Introduction: Atherosclerosis is the important cause of most cardiovascular diseases, with high prevalence and mortality. Atherosclerosis is not only a lipid metabolism disorder but also recently is defined as a chronic inflammatory disease. Several studies showed that interleukin-6 (IL-6) is involved in the pathogenesis of atherosclerosis. The aim of the present study is the examination of IL6 mRNA Levels and hypomethylation of IL6 promoter in atherosclerosis patients. Methods: In this assay, a total of 35 cases with atherosclerosis and 30 controls were enrolled. RNA and DNA were isolated from the peripheral blood of all samples. Mean IL6 gene expression was determined by RT-PCR and methylation status at six CpG motifs in IL6 promoter was determined using bisulfite genomic sequencing. Results: Real Time-PCR analysis results showed the mean IL6 RNA level in atherosclerosis patients candidate for CABG (coronary artery bypass grafting) was significantly higher than controls (P value = 0.01). Also, the upstream CpG motifs (-1038 to -952) in IL6 promoter were predominantly unmethylated in patients than in the controls (P value = 0.01). Conclusion: These findings suggest that an increase in IL-6 gene expression and its DNA hypomethylation promoter are associated with atherosclerosis patient’s candidate for CABG surgery.

Highlights

  • Atherosclerosis is the important cause of most cardiovascular diseases, with high prevalence and mortality

  • It has been well accepted that atherosclerosis is a lipid disorder and chronic inflammatory disease.[9,10]

  • Inflammation is known as an important factor in the development of atherogenesis through adverse effects on the metabolism of lipoprotein and arterial wall biology

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Summary

Introduction

Atherosclerosis is the important cause of most cardiovascular diseases, with high prevalence and mortality. It has been well accepted that atherosclerosis is a lipid disorder and chronic inflammatory disease.[9,10] Inflammation is known as an important factor in the development of atherogenesis through adverse effects on the metabolism of lipoprotein and arterial wall biology. Both innate and acquired immune system has been implicated in the atherogenic process.[9,10,11] In atherosclerosis, both immune responses (the innate and adaptive) are organized by a wide range of cytokines that control all of the disease stages. Cytokines are divided into several classes, such as the interleukins (IL), tumor necrosis factors (TNF), chemokines, transforming growth factors (TGF), the interferons (IFN), and colony-stimulating factors (CSF).[8,9,12] A large body of evidence suggests that interleukin signaling promotes atherogenic activity.[13]

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