Silencing of circARHGAP12 inhibits the progression of atherosclerosis via miR-630/EZH2/TIMP2 signal axis.

Abstract

Atherosclerosis (AS) is a common disease that seriously threatens human health. So far, the pathogenesis of AS has not been fully understood. This project investigates the effects of circARHGAP12 on ASand its regulatory mechanism. ApoE-/- knockout mice (ApoE) were adopted and reared with a high-fat diet to construct an AS model. Lentivirus was established to knock downthe expression of circARHGAP12 in mice. After 12 weeks, the aorta was removed and the expression of circARHGAP12 was detected. Vascular oil red O staining was used to detect the degree of AS. The expression of inflammatory factors was detected by ELISA. Aortic smooth muscle cells (MASMCs) were cultured to evaluate the effects of circARHGAP12 on the phenotype of MASMCs. RNA pull-down and luciferase assay were used to verify the downstream target genes of circARHGAP12. In addition, the effects of circARHGAP12 on MASMCs proliferation and migration were detected by MTT and transwell assay. Compared with the normal group, the expression of circARHGAP12 in the MASMCs under ox-LDL treatment was elevated, and circARHGAP12 silencing could inhibit AS in vitro and in vivo. The results of the mechanism study showed that circARHGAP12 can directly bind with miR-630. In addition, miR-630 can also target EZH2 to modulate the transcription of TIMP2 and to influence the migration of MASMCs. circARHGAP12 is upregulated in AS. CircARHGAP12 knockdown can inhibit the progression of AS. This study expands on the role of circRNA in AS and provides potential targets for the treatment of AS.