title: The role of miR-19b in the inhibition of endothelial cell apoptosis and its relationship with coronary artery disease.
abstract: The biological effects of microRNAs (miRNAs) and TNF-α in atherosclerosis have been widely studied. The circulating miR-17-92 cluster has been recently shown to be significantly downregulated in patients with injured vascular endothelium. However, it remains unclear whether the miR-17-92 cluster plays a significant role in vascular endothelial repair. The aim of this study was to investigate the relationship between the miR-17-92 cluster and TNF-α-induced endothelial cell apoptosis. We determined that the down-regulation of miR-19b level among patients with coronary artery disease was consistent with miRNA expression changes in endothelial cells following 24 h of TNF-α treatment. In vitro, the overexpression of miR-19b significantly alleviated the endothelial cells apoptosis, whereas the inhibition of miR-19b significantly enhanced apoptosis. The increased levels of Afap1 and caspase7 observed in our apoptosis model could be reduced by miR-19b, and this effect could be due to miR-19b binding 3'-UTRs of Afap1 and caspase7 mRNA. Therefore our results indicate that miR-19b plays a key role in the attenuation of TNF-α-induced endothelial cell apoptosis and that this function is closely linked to the Apaf1/caspase-dependent pathway.
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ya-Chen
authors.initials: YC
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Cheng-Xing
authors.initials: CX
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yi-Gang
authors.initials: YG
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D053477:Apoptotic Protease-Activating Factor 1 / Q000737:chemistry / Q000235:genetics; D001665:Binding Sites; D053179:Caspase 7 / Q000737:chemistry / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D005810:Multigene Family; D051059:PTEN Phosphohydrolase / Q000235:genetics; D034622:RNA Interference; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D053477:Apoptotic Protease-Activating Factor 1; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D051059:PTEN Phosphohydrolase; D053179:Caspase 7