Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans

Background: Aberrant vascular smooth muscle cell (VSMC) proliferation and migration contribute to the development of vascular pathologies, such as atherosclerosis and post angioplasty restenosis. The aim of this study was to determine whether miR-22-3p plays a role in regulating human artery vascular smooth muscle cell (HASMC) function and neointima formation. Methods:Quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect miR-22-3p expression in human arteries. Cell Counting Kit-8 (CCK-8) and EdU assays were performed to assess cell proliferation, and transwell and wound closure assays were performed to assess cell migration. Moreover, luciferase reporter assays were performed to identify the target genes of miR-22-3p. Finally, a rat carotid artery balloon-injury model was used to determine the role of miR-22-3p in neointima formation. Results: MiR-22-3p expression was downregulated in arteriosclerosis obliterans (ASO) arteries compared with normal arteries, as well as in platelet-derived growth factor-BB (PDGF-BB)-stimulated HASMCs compared with control cells. MiR-22-3p overexpression had anti-proliferative and anti-migratory effects and dual-luciferase assay showed that high mobility group box-1 (HMGB1) is a direct target of miR-22-3p in HASMCs. Furthermore, miR-22-3p expression was negatively correlated with HMGB1 expression in ASO tissue specimens. Finally, LV-miR-22-3p-mediated miR-22-3p upregulation significantly suppressed neointimal hyperplasia specifically by reducing HMGB1 expression in vivo. Conclusions: Our results indicate that miR-22-3p is a S. Huang and M. Wang are contributted equally to this work. key molecule in regulating HASMC proliferation and migration by targeting HMGB1 and that miR-22-3p and HMGB1 may be therapeutic targets in the treatment of human ASO. (C) 2017 The Author(s) Published by S Karger AG, Basel