miR-590-3p attenuates atherosclerosis by preventing TNF-α-induced proliferation and migration of VSMCs via NF-κB pathway

Abstract

Abstract miR-590-3p displays protective effects in some cardiovascular diseases. However, the mechanisms by which miR-590-3p regulates vascular smooth muscle cells (VSMCs) remain to be elucidated. In this study, we investigated the role of miR-590-3p/CD40/p21Cip1 pathway in VSMCs. The alterations of miR-590-3p, CD40 and /p21Cip1 were verified in atherosclerosis (AS) plaque and TNF-α treated VSMCs by quantitative Real-time PCR, EdU staining, wound healing test, and flow cytometry. The expression levels of miR-590-3p and p21Cip1 were decreased, whereas CD40 was increased in the AS plaques . TNF-α is a critical contributor of atherosclerosis and induces VSMCs proliferation and migration by upregulating CD40 and downregulating p21Cip1. miR-590-3p inhibits the proliferation and migration of VSMCs through up-regulating the expression of p21Cip1 and down-regulating the expression of CDK2/cyclin E1 by targeting CD40. The TNF-α-induced alterations were partially reversed by exogenous miR-590-3p mimic.The TNF-α-induced proliferation and migration of VSMCs were also prevented by miR-590-3p mimic . Thus, our study revealed a mechanism by which miR-590-3p attenuates atherosclerosis by preventing TNF-α-induced VSMCs proliferation and migration.