MicroRNA-424-5p regulates aortic smooth muscle cell function in atherosclerosis by blocking APOC3-mediated nuclear factor-kappa B signalling pathway

摘要

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 with the activation of inflammatory pathways as a key process in its pathogenesis. The aim of the study was 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-kappa B) signalling pathway. The results showed that miR-424-5p was poorly expressed and APOC3 highly expressed in the peripheral blood of AS patients and rat models of AS. Molecularly, our results confirmed that miR-424-5p targeted the APOC3 gene directly and inhibited APOC3 expression, which resulted in repressed activation of the NF-kappa B signalling pathway. The gain- and loss-of-function approaches were used to determine the effects of miR-424-5p and APOC3 on inflammation and on the proliferation, apoptosis and migration of aortic smooth muscle cells. Upregulation of miR-424-5p or silencing of APOC3 significantly suppressed proliferation, migration and inflammation and promoted apoptosis of aortic smooth muscle cells, which was achieved through inactivation of the NF-kappa B signalling pathway. Taken together, our results show that miR-424-5p upregulation impedes the progression of AS by blocking the APOC3-mediated NF-kappa B signalling pathway, which could be used as a novel target and a potential therapeutic pathway against AS.