Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/39551
Title: Human pericardial fluid contains exosomes enriched with cardiovascular-expressed microRNAs and promotes therapeutic angiogenesis.
Authors: Beltrami, Cristina
Besnier, Marie
Shantikumar, Saran
Shearn, Andrew I. U.
Rajakaruna, Cha
Laftah, Abas
Sessa, Fausto
Spinetti, Gaia
Petretto, Enrico
Angelini, Gianni D.
Emanueli, Costanza
First Published: 6-Jan-2016
Publisher: Elsevier (Cell Press) for American Society of Gene and Cell Therapy
Citation: Molecular Therapy
Abstract: The pericardial fluid (PF) is contained in the pericardial sac surrounding the heart. MicroRNA (miRNA) exchange via exosomes (endogenous nanoparticles) contributes to cell-to-cell communication. We investigated the hypotheses that the PF is enriched with miRNAs secreted by the heart and that it mediates vascular responses through exosome exchange of miRNAs. The study was developed using leftover material from aortic valve surgery. We found that in comparison with peripheral plasma, the PF contains exosomes enriched with miRNAs co-expressed in patients’ myocardium and vasculature. At a functional level, PF exosomes improved survival, proliferation, and networking of cultured endothelial cells (ECs) and restored the angiogenic capacity of ECs depleted (via Dicer silencing) of their endogenous miRNA content. Moreover, PF exosomes improved post-ischemic blood flow recovery and angiogenesis in mice. Mechanistically, (1) let-7b-5p is proangiogenic and inhibits its target gene, TGFBR1, in ECs; (2) PF exosomes transfer a functional let-7b-5p to ECs, thus reducing their TGFBR1 expression; and (3) let-7b-5p depletion in PF exosomes impairs the angiogenic response to these nanoparticles. Collectively, our data support the concept that PF exosomes orchestrate vascular repair via miRNA transfer.
DOI Link: 10.1016/j.ymthe.2016.12.022
ISSN: 1525-0016
eISSN: 1525-0024
Links: http://www.sciencedirect.com/science/article/pii/S1525001617300035
http://hdl.handle.net/2381/39551
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: Supplemental Information includes ten figures, three tables, raw data, and full unedited gel and can be found with this article online at http://dx.doi.org/10.1016/j.ymthe.2016.12.022.
Appears in Collections:Published Articles, Dept. of Health Sciences

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