Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Division of Medical Education, Brighton & Sussex Medical School, Brighton, UK.
IUBMB Life. 2021 Jan;73(1):223-237. doi: 10.1002/iub.2421. Epub 2020 Dec 1.
Atherosclerosis is a chronic inflammatory disease with high mortality worldwide. The reverse cholesterol transport pathway in macrophage plays an important role in the pathogenesis of coronary artery disease (CAD) and is strongly controlled by regulatory factors. The microRNAs can promote or prevent the formation of atherosclerotic lesions by post-transcriptional regulation of vital genes in this pathway. Therefore, this study was conducted to investigate the relationship between the expression levels of miR-27a, miR-329, ABCA1, and ABCG1 genes and serum levels of hs-CRP, ox-LDL, and indices of oxidative stress in the patients with established CAD and controls. A total of 84 subjects (42 patients with CAD and 42 controls) were included in this study. Expression levels of miR-27a-3p, miR-329-3p, ABCA1, and ABCG1 genes in the peripheral blood mononuclear cells (PBMCs) and serum concentration of hs-CRP and ox-LDL were measured by real time-PCR and ELISA, respectively. Also, oxidative stress parameters in the serum were evaluated by ferric-reducing antioxidant power (FRAP) and malondialdehyde (MDA) assays. ABCA1 and ABCG1 gene expression in PBMC and serum concentration of FRAP were significantly lower in the CAD group compared to the control group. Expression levels of miR-27a and miR-329 and serum levels of hs-CRP, ox-LDL, and MDA were significantly higher in the CAD group compared to the control group. Serum levels of hs-CRP, ox-LDL, and expression level of miR-27a have inversely related to ABCA1 and ABCG1 gene expression in all the subjects. An increase in the expression levels of miR-27a and miR-329 may lead to the progression of atherosclerosis plaque by downregulating the expression of ABCA1 and ABCG1 genes.
动脉粥样硬化是一种具有全球高死亡率的慢性炎症性疾病。巨噬细胞中的胆固醇逆转运途径在冠状动脉疾病 (CAD) 的发病机制中起着重要作用，并且受到调节因子的强烈控制。microRNAs 可以通过对该途径中重要基因的转录后调控来促进或阻止动脉粥样硬化病变的形成。因此，本研究旨在探讨已确诊 CAD 患者和对照组患者中 miR-27a、miR-329、ABCA1 和 ABCG1 基因的表达水平与血清 hs-CRP、ox-LDL 和氧化应激指标之间的关系。共纳入 84 例受试者（42 例 CAD 患者和 42 例对照组）。通过实时 PCR 和 ELISA 分别测量外周血单个核细胞 (PBMC) 中 miR-27a-3p、miR-329-3p、ABCA1 和 ABCG1 基因的表达水平以及血清 hs-CRP 和 ox-LDL 的浓度，通过铁还原抗氧化能力 (FRAP) 和丙二醛 (MDA) 测定评估血清中的氧化应激参数。与对照组相比，CAD 组 PBMC 中 ABCA1 和 ABCG1 基因的表达以及 FRAP 血清浓度明显降低。与对照组相比，CAD 组 miR-27a 和 miR-329 的表达水平以及血清 hs-CRP、ox-LDL 和 MDA 水平明显升高。hs-CRP、ox-LDL 血清水平与 miR-27a 的表达水平与所有受试者的 ABCA1 和 ABCG1 基因表达呈负相关。miR-27a 和 miR-329 表达水平的增加可能通过下调 ABCA1 和 ABCG1 基因的表达导致动脉粥样硬化斑块的进展。
