MiR‐424‐5p regulates aortic smooth muscle cell function in atherosclerosis by blocking APOC3‐Mediated NF‐κB signaling pathway

NEW FINDINGS: What's the role of miR-424-5p in aortic smooth muscle cells? Up-regulation of miR-424-5p inhibits inflammatory response in aortic smooth muscle cells. How does miR-424-5p function as an inflammatory response suppressor? MiR-424-5p inactivates the NF-kappaB signaling pathway through the downregulation of APOC3. ABSTRACT: Dysregulated aortic smooth muscle cells in chronic inflammation result in plaque formation in atherosclerosis (AS), which is a systemic disease that affects the large arteries, and the activation of inflammatory pathways is a key process in its pathogenesis. This study aims to investigate the regulatory mechanism of microRNA-424-5p (miR-424-5p) in aortic smooth muscle cell activities and inflammation in AS via the regulation of apolipoprotein C3 (APOC3) and the nuclear factor-kappa B (NF-kappaB) signaling pathway. The results showed that miR-424-5p was poorly expressed, and APOC3 was highly expressed in the peripheral blood of AS patients and rat models of AS. Molecularly, our results confirmed that miR-424-5p directly targeted APOC3 gene and inhibited APOC3 expression, which resulted in repressed activation of the NF-kappaB signaling pathway. The gain- and loss of function approaches were used to determine the effects of miR-424-5p and APOC3 on inflammation, and proliferation, apoptosis and migration of aortic smooth muscle cells. Up-regulation of miR-424-5p or silencing of APOC3 significantly suppresses proliferation, migration and inflammation, while promoting apoptosis of aortic smooth muscle cells, which was achieved through inactivation of the NF-kappaB signaling pathway. Taken together, miR-424-5p up-regulation impedes the progression of AS by blocking APOC3-mediated NF-kappaB signaling pathway, which could be used as a novel target and a potential therapeutic pathway against AS. This article is protected by copyright. All rights reserved.