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Human pericardial fluid contains exosomes enriched with cardiovascular-expressed microRNAs and promotes therapeutic angiogenesis
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Beltrami, Cristina, Besnier, Marie, Shantikumar, Saran, Shearn, Andrew I. U., Rajakaruna, Cha, Laftah, Abas, Sessa, Fausto, Spinetti, Gaia, Petretto, Enrico, Angelini, Gianni D. and Emanueli, Costanza (2017) Human pericardial fluid contains exosomes enriched with cardiovascular-expressed microRNAs and promotes therapeutic angiogenesis. Molecular therapy : the journal of the American Society of Gene Therapy, 25 (3). pp. 679-693. doi:10.1016/j.ymthe.2016.12.022
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Official URL: https://doi.org/10.1016/j.ymthe.2016.12.022
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.
| Item Type: | Journal Article | ||||||||
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| Divisions: | Faculty of Medicine > Warwick Medical School | ||||||||
| Journal or Publication Title: | Molecular therapy : the journal of the American Society of Gene Therapy | ||||||||
| Publisher: | Elsevier | ||||||||
| ISSN: | 1525-0024 | ||||||||
| Official Date: | 1 March 2017 | ||||||||
| Dates: |
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| Volume: | 25 | ||||||||
| Number: | 3 | ||||||||
| Page Range: | pp. 679-693 | ||||||||
| DOI: | 10.1016/j.ymthe.2016.12.022 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access |
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