Open AccessAn Agomir of miR-144-3p Accelerates Plaque Formation through Impairing Reverse Cholesterol Transport and Promoting Pro-Inflammatory Cytokine Production
Author(s) -
YanWei Hu,
Ya-Rong Hu,
Jiayi Zhao,
Shufen Li,
Xin Ma,
Shao-Guo Wu,
Jing-Bo Lu,
Yurong Qiu,
Yan-Hua Sha,
Yanchao Wang,
Ji-Juan Gao,
Lei Zheng,
Qian Wang
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0094997
Subject(s) - abca1 , reverse cholesterol transport , cholesterol , in vivo , western blot , efflux , lipid metabolism , inflammation , cytokine , transfection , biology , microrna , proinflammatory cytokine , liver x receptor , gene knockdown , chemistry , pharmacology , transporter , biochemistry , immunology , lipoprotein , apoptosis , microbiology and biotechnology , gene , nuclear receptor , transcription factor
Aims ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins, which then form nascent HDL, a key step in the mechanism of reverse cholesterol transport (RCT). While a series of microRNAs (miRNAs) have been identified as potent post-transcriptional regulators of lipid metabolism, their effects on ABCA1 function and associated mechanisms remain unclear. Methods and Results ABCA1 was identified as a potential target of miR-144-3p, based on the results of bioinformatic analysis and the luciferase reporter assay, and downregulated after transfection of cells with miR-144-3p mimics, as observed with real-time PCR and western blot. Moreover, miR-144-3p mimics (agomir) enhanced the expression of inflammatory factors, including IL-1β, IL-6 and TNF-α, in vivo and in vitro , inhibited cholesterol efflux in THP-1 macrophage-derived foam cells, decreased HDL-C circulation and impaired RCT in vivo , resulting in accelerated pathological progression of atherosclerosis in apoE −/− mice. Clinical studies additionally revealed a positive correlation of circulating miR-144-3p with serum CK, CK-MB, LDH and AST in subjects with AMI. Conclusions Our findings clearly indicate that miR-144-3p is essential for the regulation of cholesterol homeostasis and inflammatory reactions, supporting its utility as a potential therapeutic target of atherosclerosis and a promising diagnostic biomarker of AMI.