MicroRNA-194 acts as a suppressor during abdominal aortic aneurysm via inhibition of KDM3A-mediated BNIP3

Abstract

Aims: Abdominal aortic aneurysm (AAA) is a serious disorder with a high disability rates and mortality rates. Accumulating evidence has identified the vital functions of microRNAs (miRNAs) in the treatment of AAA. Hence, this study is aimed at exploring the modulatory role of miR-194 in the development of AAA.

Main methods: After the establishment of mouse AAA models, the expression of miR-194 was determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR), while lysine demethylase 3A (KDM3A) was determined by Western blot analysis in vascular smooth muscle cells (VSMCs) from the abdominal aorta. Cell apoptosis, levels of inflammatory factors as well as expressions of matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9) were measured after altering the expression of miR-194 and KDM3A in VSMCs. Moreover, the interactions among miR-194, KDM3A, and BCL2 interacting protein 3 (BNIP3) were investigated by chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter gene assay.

Key findings: miR-194 was poorly expressed while the expression of KDM3A was up-regulated in mice with AAA. miR-194 inhibited the expression of KDM3A while BNIP3 was positively mediated by KDM3A. More importantly, the number of macrophages was significantly reduced whereas the rate of apoptosis in VSMCs was enhanced. miR-194 reduced the inflammatory response and oxidative stress by repressing KDM3A-mediated BNIP3 expression.

Significances: miR-194 played a suppressive role in the progression of AAA by inhibiting the expression of BNIP3 via KDM3A, representing a promising target for AAA management.

Keywords: Abdominal aortic aneurysm; BNIP3; Histone demethylase; KDM3A; MicroRNA-194; Mouse model; Vascular smooth muscle cell.