MicroRNA-32 promotes calcification in vascular smooth muscle cells: Implications as a novel marker for coronary artery calcification.
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.
Institute of Clinical Medicine, the First Affiliated Hospital of University of South China, Hengyang, People's Republic of China (PRC).|Department of Metabolism and Endocrinology, the First Affiliated Hospital of University of South China, Hengyang, PRC.
Jianghua
J
Liu
Department of Metabolism and Endocrinology, the First Affiliated Hospital of University of South China, Hengyang, PRC.
Xinhua
X
Xiao
Institute of Clinical Medicine, the First Affiliated Hospital of University of South China, Hengyang, People's Republic of China (PRC).
Yingying
Y
Shen
Institute of Clinical Medicine, the First Affiliated Hospital of University of South China, Hengyang, People's Republic of China (PRC).
Ling
L
Chen
Department of Pathology and Immunology, University of Washington School of Medicine, St. Louis, Missouri, United States of America.
Canxin
C
Xu
Department of Metabolism and Endocrinology, the First Affiliated Hospital of University of South China, Hengyang, PRC.
Heng
H
Zhao
Institute of Clinical Medicine, the First Affiliated Hospital of University of South China, Hengyang, People's Republic of China (PRC).
Ying
Y
Wu
Institute of Clinical Medicine, the First Affiliated Hospital of University of South China, Hengyang, People's Republic of China (PRC).
Qinghai
Q
Zhang
Institute of Clinical Medicine, the First Affiliated Hospital of University of South China, Hengyang, People's Republic of China (PRC).
Jing
J
Zhong
Department of Cardiovascular Medicine, the First Affiliated Hospital of University of South China, Hengyang, PRC.
Zhenwang
Z
Tang
Department of Cardiovascular Medicine, the First Affiliated Hospital of University of South China, Hengyang, PRC.
Changhui
C
Liu
Department of Metabolism and Endocrinology, the First Affiliated Hospital of University of South China, Hengyang, PRC.
Qiang
Q
Zhao
Department of Metabolism and Endocrinology, the First Affiliated Hospital of University of South China, Hengyang, PRC.
Yi
Y
Zheng
Institute of Clinical Medicine, the First Affiliated Hospital of University of South China, Hengyang, People's Republic of China (PRC).|Department of Metabolism and Endocrinology, the First Affiliated Hospital of University of South China, Hengyang, PRC.
Renxian
R
Cao
Institute of Clinical Medicine, the First Affiliated Hospital of University of South China, Hengyang, People's Republic of China (PRC).
Xuyu
X
Zu
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D061205:Vascular Calcification / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; C568529:MIRN32 microRNA, human; C575616:MIRN32 microRNA, mouse; D035683:MicroRNAs; D053244:Osteoprotegerin; C493716:Runx2 protein, mouse; C506031:Tnfrsf11b protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse