Effect of miR-663 on atherosclerosis by regulating the proliferation of vascular smooth muscle cells in lipid plaques.

Abstract

Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease. microRNAs (miRNAs) are widely distributed in the human body and closely related to the pathological progress of AS. This study probed into the function of miR-663 in AS. The atherosclerotic plaques, cholesterol (CHOL), low-density lipoprotein (LDL), inflammatory factors, and miR-663 expression in ApoE-/- mice on high-fat diet were evaluated. The overexpressing miR-663 adenovirus was injected into ApoE-/- mice, followed by measurement of type III collagen (Col III), matrix metalloproteinase (MMP)-2, α-SMA, osteopontin, and CD31. miR-663 mimic or inhibitor was introduced into vascular smooth muscle cells (VSMCs) stimulated by oxidized LDL (Ox-LDL), and cell proliferation and IL-6 and IL-18 secretion were evaluated. The binding relationship between miR-663 and HMGA2 was verified, followed by the determination of HMGA2 role in VSMC proliferation. Atherosclerotic plaques appeared in ApoE-/- mice on high-fat diet, with increased CHOL, LDL, osteopontin, MMP-2 and Col III and decreased miR-663, α-SMA and CD31. miR-663 overexpression downregulated osteopontin, MMP-2 and Col III and upregulated α-SMA and CD31 in ApoE-/- mice on high-fat diet. With Ox-LDL concentration increase, VSMC proliferation was promoted and miR-663 was downregulated. miR-663 overexpression inhibited proliferation of Ox-LDL-stimulated VSMCs and reduced levels of inflammatory factor levels, whereas silencing miR-663 did the opposite. miR-663 targeted HMGA2. HMGA2 overexpression partially reversed the inhibitory effect of miR-663 overexpression on VSMC proliferation. miR-663 targeted HMGA2 to inhibit VSMC proliferation and AS development, which may offer insights into AS treatment.