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

Abstract：

NEW FINDINGS:What 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.

journal_name

Exp Physiol

journal_title

Experimental physiology

authors

Li C,Zhang M,Dai Y,Xu Z

doi

10.1113/EP088088

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

1035-1049

issue

eissn

0958-0670

issn

1469-445X

journal_volume

105

pub_type

杂志文章

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