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Title: | MicroRNA-216a is essential for cardiac angiogenesis | Authors: | Juni, Rio P. Kocken, Jordy M. M. Abreu, Ricardo C. Ottaviani, Lara Davalan, Tim Duygu, Burcu Poels, Ella M. Vasilevich, Aliaksei Hegenbarth, Jana C. Appari, Mahesh Bitsch, Nicole Olieslagers, Serve Schrijvers, Dorien M. Stoll, Monika Heineke, Joerg de Boer, Jan de Windt, Leon J. da Costa Martins, Paula A. |
Keywords: | angiogenesis; autophagy; cardiac remodeling; endothelial cells; heart failure; microRNAs | Issue Date: | 7-Jun-2023 | Publisher: | Elsevier | Project: | A.V. acknowledges the financial support of the European Union’s Seventh Framework (FP7/2007-2013) grant agreement 289720. J.D.B. acknowledges the financial support of the Dutch province of Limburg. L.D.W. acknowledges support from the Netherlands Cardiovascular Research Initiative and the Dutch Heart Foundation, the Netherlands. L.D.W. was further supported by grant 311549 from the European Research Council (ERC) and a VICI award 918-156-47 from The Netherlands Organization for Scientific Research (NWO). P.C.M. is supported by a MEERVOUD grant from The Netherlands Organization for Scientific Research (NWO), a Dutch CardioVascular Alliance (DCVA) awarded to the Phaedra consortium, as well as the Impulse Grant 2018 awarded to the Phaedra IMPACT consortium (CVON-2018-29), and is an Established Investigator of the Dutch Heart Foundation (NHS2015T066). P.C.M. and R.C.A. were further supported by the H2020 Twinning project RESETageing (GA 952266). J.M.M.K. was supported by a Dutch CardioVascular Alliance (DCVA) awarded to the Phaedra consortium as well as the Impulse Grant 2018 awarded to the Phaedra IMPACT consortium (CVON-2018-29). | Serial title, monograph or event: | Molecular Therapy | Volume: | 31 | Issue: | 6 | Abstract: | While it is experimentally supported that impaired myocardial vascularization contributes to a mismatch between myocardial oxygen demand and supply, a mechanistic basis for disruption of coordinated tissue growth and angiogenesis in heart failure remains poorly understood. Silencing strategies that impair microRNA biogenesis have firmly implicated microRNAs in the regulation of angiogenesis, and individual microRNAs prove to be crucial in developmental or tumor angiogenesis. A high-throughput functional screening for the analysis of a whole-genome microRNA silencing library with regard to their phenotypic effect on endothelial cell proliferation as a key parameter, revealed several anti- and pro-proliferative microRNAs. Among those was miR-216a, a pro-angiogenic microRNA which is enriched in cardiac microvascular endothelial cells and reduced in expression under cardiac stress conditions. miR-216a null mice display dramatic cardiac phenotypes related to impaired myocardial vascularization and unbalanced autophagy and inflammation, supporting a model where microRNA regulation of microvascularization impacts the cardiac response to stress. | URI: | https://hdl.handle.net/10316/112353 | ISSN: | 15250016 | DOI: | 10.1016/j.ymthe.2023.04.007 | Rights: | openAccess |
Appears in Collections: | I&D CIBB - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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