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

Abstract

Objectives 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. Methods 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. Results 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. Conclusion miR-663 targeted HMGA2 to inhibit VSMC proliferation and AS development, which may offer insights into AS treatment.

High glucose promotes atherosclerosis by regulating miRNA let7d‐5p level

“…More research is required to determine the precise mechanism by which HMGA2 influences Gsk3β phosphorylation. It has been proven in recent years that HMGA2 is involved in the proliferation and growth of VSMCs 54 , 55 and associated with diabetic nephropathy, atherosclerosis, and cancer 37 , 56 , 57 . These findings indicate the key role of HMGA2 in the let‐7d‐5p induced‐activation of GSK3β/β‐catenin pathway, and let‐7d‐5p may represent a novel target for diabetes‐related plaque formation prevention measures.…”

Anti-atherosclerosis mechanisms associated with regulation of non-coding RNAs by active monomers of traditional Chinese medicine

“…Frontiers in Pharmacology frontiersin.org (Deng and Li, 2022). In conclusion, miRNAs regulate atherosclerosis through affecting the function of endothelial cells, macrophages, and VSMCs.…”

Circ_0091822 Contributes to the Proliferation, Invasion, and Migration of Vascular Smooth Muscle Cells Under Oxidized Low-Density Lipoprotein Treatment

“…Studies have shown that plaque formation of AS involves a variety of factors, including vascular smooth muscle cells (VSMCs) abnormal proliferation (2,3). Abnormal proliferation of VSMCs is considered to be an important step in the development of AS, which can lead to arterial wall thickening and the formation of lipid plaques (4,5). Therefore, exploring the molecular mechanisms influencing VSMCs proliferation and migration may help us develop potential molecular targets for AS therapy.…”