Intercellular transfer of miR-200c-3p impairs the angiogenic capacity of cardiac endothelial cells

Lara Ottaviani, Rio P. Juni, Ricardo C. de Abreu, Marida Sansonetti, Vasco Sampaio-Pinto, Julie Halkein, Jana C. Hegenbarth, Nadja Ring, Kevin Knoops, Jordy M. M. Kocken, Carlos de Jesus, Auriane C. Ernault, Hamid el Azzouzi, Frank Rühle, Servé Olieslagers, Hugo Fernandes, Lino Ferreira, Luca Braga, Monika Stoll, Diana S. NascimentoLeon J. de Windt, Paula A. da Costa Martins*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)2257-2273
Number of pages17
JournalMolecular Therapy
Issue number6
Early online date2022
Publication statusPublished - 1 Jun 2022

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