PMID- 25656649 OWN - NLM STAT- MEDLINE DCOM- 20150715 LR - 20181113 IS - 1097-4652 (Electronic) IS - 0021-9541 (Print) IS - 0021-9541 (Linking) VI - 230 IP - 8 DP - 2015 Aug TI - MicroRNA-214 Is Upregulated in Heart Failure Patients and Suppresses XBP1-Mediated Endothelial Cells Angiogenesis. PG - 1964-73 LID - 10.1002/jcp.24942 [doi] AB - More and more miRNAs have been shown to regulate gene expression in the heart and dysregulation of their expression has been linked to cardiovascular diseases including the miR-199a/214 cluster. However, the signature of circulating miR-214 expression and its possible roles during the development of heart failure has been less well studied. In this study, we elucidated the biological and clinical significance of miR-214 dysregulation in heart failure. Firstly, circulating miR-214 was measured by quantitative PCR, and we found that miR-214 was upregulated in the serum of chronic heart failure patients, as well as in hypertrophic and failing hearts of humans and mice. Adeno-associated virus serotype 9 (AAV9)-mediated miR-214 silencing attenuates isoproterenol (ISO) infusion-induced cardiac dysfunction and impairment of cardiac angiogenesis in mice. Mechanistically, miR-214 overexpression reduces angiogenesis of HUVECs by targeting XBP1, an important transcription factor of unfolded protein response, and XBP1 silencing decreases HUVECs proliferation and angiogenesis similar to miR-214 overexpression. Furthermore, ectopic expression of XBP1 enhances endothelial cells proliferation and tube formation, and reverses anti-angiogenic effect of miR-214 over expression. All these findings suggest that miR-214 is an important regulator of angiogenesis in heart in vitro and in vivo, likely via regulating the expression of XBP1, and demonstrate that miR-214 plays an essential role in the control/inhibition of cardiac angiogenesis. CI - (c) 2015 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc. FAU - Duan, Quanlu AU - Duan Q AD - Department Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. FAU - Yang, Lei AU - Yang L FAU - Gong, Wei AU - Gong W FAU - Chaugai, Sandip AU - Chaugai S FAU - Wang, Feng AU - Wang F FAU - Chen, Chen AU - Chen C FAU - Wang, Peihua AU - Wang P FAU - Zou, Ming-Hui AU - Zou MH FAU - Wang, Dao Wen AU - Wang DW LA - eng GR - R01 HL089920/HL/NHLBI NIH HHS/United States GR - R01 HL128014/HL/NHLBI NIH HHS/United States GR - R01 HL074399/HL/NHLBI NIH HHS/United States GR - R01 AG047776/AG/NIA NIH HHS/United States GR - R01 HL110488/HL/NHLBI NIH HHS/United States GR - R01 HL105157/HL/NHLBI NIH HHS/United States GR - R01 HL079584/HL/NHLBI NIH HHS/United States GR - R01 HL080499/HL/NHLBI NIH HHS/United States GR - R01 HL096032/HL/NHLBI NIH HHS/United States GR - R01 HL132500/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (DNA-Binding Proteins) RN - 0 (MIRN214 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Regulatory Factor X Transcription Factors) RN - 0 (Transcription Factors) RN - 0 (X-Box Binding Protein 1) RN - 0 (XBP1 protein, human) RN - 0 (Xbp1 protein, mouse) SB - IM MH - Aged MH - Animals MH - Blotting, Western MH - DNA-Binding Proteins/*metabolism MH - Endothelial Cells/*metabolism MH - Female MH - Gene Expression Regulation/physiology MH - Gene Knockdown Techniques MH - Heart Failure/*genetics/metabolism MH - Humans MH - Immunohistochemistry MH - Male MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*metabolism MH - Middle Aged MH - Neovascularization, Physiologic/*genetics MH - Real-Time Polymerase Chain Reaction MH - Regulatory Factor X Transcription Factors MH - Transcription Factors/*metabolism MH - Up-Regulation MH - X-Box Binding Protein 1 PMC - PMC4911176 MID - NIHMS790394 EDAT- 2015/02/07 06:00 MHDA- 2015/07/16 06:00 PMCR- 2016/09/20 CRDT- 2015/02/07 06:00 PHST- 2013/11/21 00:00 [received] PHST- 2015/01/23 00:00 [accepted] PHST- 2015/02/07 06:00 [entrez] PHST- 2015/02/07 06:00 [pubmed] PHST- 2015/07/16 06:00 [medline] PHST- 2016/09/20 00:00 [pmc-release] AID - JCP24942 [pii] AID - 10.1002/jcp.24942 [doi] PST - ppublish SO - J Cell Physiol. 2015 Aug;230(8):1964-73. doi: 10.1002/jcp.24942.