Open AccessMicroRNA-32 promotes calcification in vascular smooth muscle cells: Implications as a novel marker for coronary artery calcification
Author(s) -
Jianghua Liu,
Xinhua Xiao,
Yingying Shen,
Ling Chen,
Chenghai Xu,
Heng Zhao,
Ying Wu,
Qinghai Zhang,
Jing Zhong,
Zhenwang Tang,
Changhui Liu,
Qiang Zhao,
Yi Zheng,
Renxian Cao,
Xuyu Zu
Publication year - 2017
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.0174138
Subject(s) - osteopontin , vascular smooth muscle , tensin , pten , microrna , calcification , cancer research , runx2 , medicine , biology , pi3k/akt/mtor pathway , pathology , signal transduction , microbiology and biotechnology , transcription factor , biochemistry , smooth muscle , gene
Cardiovascular calcification is one of the most severe outcomes associated with cardiovascular disease and often results in significant morbidity and mortality. Previous reports indicated that epigenomic regulation of microRNAs (miRNAs) might play important roles in vascular smooth muscle cell (VSMC) calcification. Here, we identified potential key miRNAs involved in vascular calcification in vivo and investigated the role of miR-32-5p (miR-32). According to microarray analysis, we observed increased expression of miR-125b, miR-30a, and miR-32 and decreased expression of miR-29a, miR-210, and miR-320 during the progression of vascularcalcification. Additionally, gain- and loss-of-function studies of miR-32 confirmed promotion of VSMC calcification in mice through the enhanced expression of bonemorphogenetic protein-2, runt-related transcription factor-2(RUNX2), osteopontin, and the bone-specific phosphoprotein matrix GLA protein in vitro . Moreover, miR-32 modulated vascularcalcification progression by activating phosphoinositide 3-kinase (PI3K)signaling and increasing RUNX2 expression and phosphorylation by targeting the 3′-untranslated region of phosphatase and tensin homolog Mrna (PTEN) in mouse VSMCs. Furthermore, we detected higher miR-32 levels in plasmafrom patients with coronary artery disease with coronary artery calcification (CAC) as compared with levels observed in non-CAC patients ( P = 0.016), further confirming miR-32 as a critical modulator and potential diagnostic marker for CAC.