Open AccessY RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL ‐10 expression and secretion
Author(s) -
Cambier Linda,
Couto Geoffrey,
Ibrahim Ahmed,
Echavez Antonio K,
Valle Jackelyn,
Liu Weixin,
Kreke Michelle,
Smith Rachel R,
Marbán Linda,
Marbán Eduardo
Publication year - 2017
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201606924
Subject(s) - chemistry , secretion , extracellular , microbiology and biotechnology , recombinant dna , biochemistry , biology , gene
Cardiosphere‐derived cells ( CDC s) reduce myocardial infarct size via secreted extracellular vesicles ( CDC ‐EVs), including exosomes, which alter macrophage polarization. We questioned whether short non‐coding RNA species of unknown function within CDC ‐EVs contribute to cardioprotection. The most abundant RNA species in CDC ‐EVs is a Y RNA fragment (EV‐ YF 1); its relative abundance in CDC ‐EVs correlates with CDC potency in vivo . Fluorescently labeled EV‐ YF 1 is actively transferred from CDC s to target macrophages via CDC ‐EVs. Direct transfection of macrophages with EV‐ YF 1 induced transcription and secretion of IL ‐10. When cocultured with rat cardiomyocytes, EV‐ YF 1‐primed macrophages were potently cytoprotective toward oxidatively stressed cardiomyocytes through induction of IL ‐10. In vivo, intracoronary injection of EV‐ YF 1 following ischemia/reperfusion reduced infarct size. A fragment of Y RNA , highly enriched in CDC ‐EVs, alters Il10 gene expression and enhances IL ‐10 protein secretion. The demonstration that EV‐ YF 1 confers cardioprotection highlights the potential importance of diverse exosomal contents of unknown function, above and beyond the usual suspects (e.g., micro RNA s and proteins).