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. Researchers at the University of Bristol 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. They 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, these data support the concept that PF exosomes orchestrate vascular repair via miRNA transfer.
Pericardial fluid exosomes orchestrate vascular repair via microRNA transfer
Beltrami C, Besnier M, Shantikumar S, Shearn AI, Rajakaruna C, Laftah A, Sessa F, Spinetti G, Petretto E, Angelini GD, Emanueli C. (2017) Human Pericardial Fluid Contains Exosomes Enriched with Cardiovascular-Expressed MicroRNAs and Promotes Therapeutic Angiogenesis. Mol Ther [Epub ahead of print]. [article]