Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL-10 expression and secretion.
Cardiosphere-derived cells (CDCs) 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-YF1); its relative abundance in CDC-EVs correlates with CDC potencyin vivoFluorescently labeled EV-YF1 is actively transferred from CDCs to target macrophages via CDC-EVs. Direct transfection of macrophages with EV-YF1 induced transcription and secretion of IL-10. When cocultured with rat cardiomyocytes, EV-YF1-primed macrophages were potently cytoprotective toward oxidatively stressed cardiomyocytes through induction of IL-10.In vivo,intracoronary injection of EV-YF1 following ischemia/reperfusion reduced infarct size. A fragment of Y RNA, highly enriched in CDC-EVs, altersIl10gene expression and enhances IL-10 protein secretion. The demonstration that EV-YF1 confers cardioprotection highlights the potential importance of diverse exosomal contents of unknown function, above and beyond the usual suspects (e.g., microRNAs and proteins).
Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Linda
L
Cambier
Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Geoffrey
G
de Couto
Capricor Inc., Los Angeles, CA, USA.
Ahmed
A
Ibrahim
Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Antonio K
AK
Echavez
Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Jackelyn
J
Valle
Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Weixin
W
Liu
Capricor Inc., Los Angeles, CA, USA.
Michelle
M
Kreke
Capricor Inc., Los Angeles, CA, USA.
Rachel R
RR
Smith
Capricor Inc., Los Angeles, CA, USA.
Linda
L
Marbán
Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA eduardo.marban@cshs.org.
Eduardo
0000-0002-3863-280X
E
Marbán
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D000067128:Extracellular Vesicles / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D009203:Myocardial Infarction / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D020733:RNA, Small Cytoplasmic / Q000008:administration & dosage / Q000378:metabolism*; D017208:Rats, Wistar; D016896:Treatment Outcome
D020733:RNA, Small Cytoplasmic; D016753:Interleukin-10

RNA
; extracellular vesicle; macrophage; stem cells