@article{3fc2ea1e3955413cade6bb2ce08b60c3,
title = "Intercellular transfer of miR-200c-3p impairs the angiogenic capacity of cardiac endothelial cells",
abstract = "As mediators of intercellular communication, extracellular vesicles containing molecular cargo, such as microRNAs, are secreted by cells and taken up by recipient cells to influence their cellular phenotype and function. Here we report that cardiac stress-induced differential microRNA content, with miR-200c-3p being one of the most enriched, in cardiomyocyte-derived extracellular vesicles mediates functional cross-talk with endothelial cells. Silencing of miR-200c-3p in mice subjected to chronic increased cardiac pressure overload resulted in attenuated hypertrophy, smaller fibrotic areas, higher capillary density, and preserved cardiac ejection fraction. We were able to maximally rescue microvascular and cardiac function with very low doses of antagomir, which specifically silences miR-200c-3p expression in non-myocyte cells. Our results reveal vesicle transfer of miR-200c-3p from cardiomyocytes to cardiac endothelial cells, underlining the importance of cardiac intercellular communication in the pathophysiology of heart failure.",
keywords = "cardiac angiogenesis, cardiac remodeling, extracellular vesicles, intercellular communication, microRNAs",
author = "Lara Ottaviani and Juni, {Rio P} and {de Abreu}, {Ricardo C} and Marida Sansonetti and Vasco Sampaio-Pinto and Julie Halkein and Hegenbarth, {Jana C} and Nadja Ring and Kevin Knoops and Kocken, {Jordy M M} and Jesus, {Carlos de} and Ernault, {Auriane C} and {El Azzouzi}, Hamid and Frank R{\"u}hle and Serv{\'e} Olieslagers and Hugo Fernandes and Lino Ferreira and Luca Braga and Monika Stoll and Nascimento, {Diana S} and {de Windt}, {Leon J} and {da Costa Martins}, {Paula A}",
note = "Funding Information: L.J.d.W. acknowledges support from the Netherlands CardioVascular Research Initiative : the Dutch Heart Foundation , Dutch Federation of University Medical Centers , ZonMw , and the Royal Netherlands Academy of Sciences ( CVON2017-ARENA PRIME ). L.J.d.W. was also supported by ERC Consolidator Grant 311549 CALMIRS and VICI Award 918-156-47 from NWO . J.M.M.K. and P.A.d.C.M. were supported by the Dutch CardioVascular Alliance (DCVA) awarded to the Phaedra Consortium as well as the Impulse Grant 2018 awarded to the Phaedra IMPACT Consortium ( 2012-08 , 2014-11 ). L.O. and P.d.C.M. were supported by a Dutch Heart Foundation grant ( NHS2015T066 ). V.S.-P. and R.C.d.A. were supported by Foundation for Science and Technology of Portugal (FCT) grants ( SFRH/BD/111799/2015 and SFRH/BD/129317/2017 , respectively). D.N. was supported by a Foundation for Science and Technology of Portugal (FCT) grant ( POCI-01-0145-FEDER-030985 ). This work was also partially supported by the H2020 Twinning project RESETageing ( GA 952266 ). We are grateful to the Core Facility Genomics (CFG) of the Medical Faculty of the University of M{\"u}nster, Germany, for performing RNA sequencing and helping with data analysis. Funding Information: L.J.d.W. acknowledges support from the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centers, ZonMw, and the Royal Netherlands Academy of Sciences (CVON2017-ARENA PRIME). L.J.d.W. was also supported by ERC Consolidator Grant 311549 CALMIRS and VICI Award 918-156-47 from NWO. J.M.M.K. and P.A.d.C.M. were supported by the Dutch CardioVascular Alliance (DCVA) awarded to the Phaedra Consortium as well as the Impulse Grant 2018 awarded to the Phaedra IMPACT Consortium (2012-08, 2014-11). L.O. and P.d.C.M. were supported by a Dutch Heart Foundation grant (NHS2015T066). V.S.-P. and R.C.d.A. were supported by Foundation for Science and Technology of Portugal (FCT) grants (SFRH/BD/111799/2015 and SFRH/BD/129317/2017, respectively). D.N. was supported by a Foundation for Science and Technology of Portugal (FCT) grant (POCI-01-0145-FEDER-030985). This work was also partially supported by the H2020 Twinning project RESETageing (GA 952266). We are grateful to the Core Facility Genomics (CFG) of the Medical Faculty of the University of M{\"u}nster, Germany, for performing RNA sequencing and helping with data analysis. L.O. R.P.J. D.S.N. R.C.d.A. and P.A.d.C.M. conceived and planned the experiments. L.O. R.P.J. M.S. J.H. R.C.d.A. H.e.A. C.d.J. and D.S.N. carried out the experiments. V.S.-P. A.C.E. J.M.M.K. H.F. and S.O. contributed to sample preparation and analysis. L.O. R.P.J. V.S.-P. L.F. D.S.N. L.J.d.W. and P.A.d.C.M. contributed to the interpretation of the results. K.K. contributed to imaging acquisition and the respective data analysis. F.R. J.C.H. and M.S. contributed to the RNA sequencing data and respective analysis. J.C.H. contributed to RNA sequencing data analysis and visualization. L.O. R.P.J. and P.A.d.C.M. wrote the manuscript. P.A.d.C.M. supervised the execution and development of the project. All authors provided critical feedback and helped shape the research, analysis, and manuscript. L.J.d.W. and P.A.d.C.M. are cofounders of Mirabilis Therapeutics. Publisher Copyright: {\textcopyright} 2022 The American Society of Gene and Cell Therapy",
year = "2022",
month = jun,
day = "1",
doi = "10.1016/j.ymthe.2022.03.002",
language = "English",
volume = "30",
pages = "2257--2273",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "6",
}