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MicroRNA‐424‐5p regulates aortic smooth muscle cell function in atherosclerosis by blocking APOC3‐mediated nuclear factor‐κB signalling pathway
Author(s) -
Li Chuanfang,
Zhang Meng,
Dai Yuchuan,
Xu Zesheng
Publication year - 2020
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/ep088088
Subject(s) - downregulation and upregulation , inflammation , gene silencing , microrna , microbiology and biotechnology , vascular smooth muscle , signal transduction , chemistry , medicine , endocrinology , cancer research , biology , smooth muscle , biochemistry , gene
New FindingsWhat is the central question of this study? What is the role of microRNA‐424‐5p (miR‐424‐5p) in aortic smooth muscle cells? How does miR‐424‐5p function as a suppressor of the inflammatory response?What is the main finding and its importance? Upregulation of miR‐424‐5p inhibits the inflammatory response in aortic smooth muscle cells. miR‐424‐5p inactivates the nuclear factor‐κB signalling pathway through the downregulation of apolipoprotein C3.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 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‐κB (NF‐κB) 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‐κB 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‐κB signalling pathway. Taken together, our results show that miR‐424‐5p upregulation impedes the progression of AS by blocking the APOC3‐mediated NF‐κB signalling pathway, which could be used as a novel target and a potential therapeutic pathway against AS.