MiR‑30e and miR‑92a are related to atherosclerosis by targeting ABCA1

Abstract

Atherosclerosis is a chronic disease characterized by the accumulation of lipids and fibrous elements in the large arteries, which is the principal cause of coronary artery disease. Dysregulated exosomal microRNA (miRNA) levels in serum have been identified in patients with various diseases, including CAD. In the present study, nine candidate miRNAs were detected in the plasma exosome from 42 patients with coronary atherosclerosis, and a higher expression of miR-30e and miR-92a was identified in patients. Following bioinformatics analysis and confirmation through immunoblotting, it was demonstrated that ATP binding cassette (ABC)A1 is a direct target of miR-30e, and miR-92a. Furthermore, a negative correlation was identified between plasma miR-30e and ABCA1, or miR-30e and cholesterol. Thus, the results of the present study suggest that the miR-30e level in exosomes from serum may have the potential to be a novel diagnostic biomarker for coronary atherosclerosis.

The crosstalk: exosomes and lipid metabolism

“…Specific knockout of ABCA1 or ABCG1 in macrophages and vascular smooth muscle cells (VSMCs) respectively promotes foam cell formation in LDLR −/− mice due to deficient cholesterol efflux. Some circulating miRNAs in exosomes, such as miR-30e and miR-92a, display inhibitory effects on ABCA1 and ABCG1, causing the intracellular accumulation of cholesterol [58]. Exosomes with HIV-1 protein Nef (exNef) can be rapidly uptake by macrophages, and subsequently release exNef into cells, resulting in down-regulation of ABCA1, reduction of cholesterol efflux and a sharp elevation of in the abundance of lipid rafts through reducing the activation of small GTPase Cdc42 and decreasing actin polymerization exosomes with exNef can be rapidly uptake by macrophages, rapidly, and then exNef is released into the cells, resulting in down-regulation of ABCA1 and inactivation of small GTPase Cdc42 as well as reduction of actin polymerization [59].…”

Interaction Between microRNA and DNA Methylation in Atherosclerosis

“…MiR92a is an important member of the miR92 family; it participates in many AS processes and even regulates chronic kidney disease-induced CAD (Wiese et al, 2019). MiR92a expression is increased in patients with CAD, and it could regulate cholesterol levels by binding with ABCA1 (Wang et al, 2019c). Histone methylation could be regulated by histone methyltransferases, thereby activating or inhibiting the expression of related genes (Weinberg et al, 2019).…”

“…It mainly inhibits the expression of related genes by methylating the histone H3K27 methylation site ( Jiao and Liu, 2015). MiR92a is closely related to AS development (Liu et al, 2018a;Wang et al, 2019c). Another notable detail is that miR92a overexpression could inhibit the increase in histone methyltransferase enhancer of Zeste homolog 2 (EZH2) through target binding, thereby reducing H3K27me3 and lipid levels in foam cell (Xiaoling et al, 2016).…”

MicroRNAs as Therapeutic Targets and Clinical Biomarkers in Atherosclerosis

“…Inhibition of miR-33a/b enhanced cholesterol efflux and regression of atherosclerotic plaques in Ldlr −/− mice [24] and improved lipid profiles in non-human primates [25,26]. Other miRNAs including miR-144, miR-27a/b, miR-302a, miR-148a, miR-92a, miR-30e, miR-101, miR-23a-5p, miR-20a/b and miR-10b also target cholesterol transporters (LDLR and ABCA1) [19,[27][28][29][30][31][32][33][34], highlighting their potential in regulating atherosclerosis. Cholesterol-loaded mature HDL facilitates the removal or redistribution of cholesterol via its uptake in the liver through SR-BI.…”

“…Cholesterol-loaded mature HDL facilitates the removal or redistribution of cholesterol via its uptake in the liver through SR-BI. In atherosclerosis, miR-185, miR-96, miR-223 and miR-24 target hepatic SR-BI to suppress HDL uptake in the liver, preventing cholesterol excretion by the liver [15,17,30,35]. miR-24 was further shown to contribute to plaque progression, promoting lipid accumulation in the liver [17,36].…”