RT Journal Article
SR Electronic
T1 Red blood cell-derived extracellular vesicles mediate intercellular communication in ischemic heart failure
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 624841
DO 10.1101/624841
A1 Avash Das
A1 Nedyalka Valkov
A1 Ane M. Salvador
A1 Ivan Kur
A1 Olivia Ziegler
A1 Ashish Yeri
A1 Fernando Camacho Garcia
A1 Shulin Lu
A1 Aushee Khamesra
A1 Chunyang Xiao
A1 Rodosthenis Rodosthenous
A1 Guoping Li
A1 Srimeenakshi Srinivasan
A1 Vasilis Toxavidis
A1 John Tigges
A1 Louise C. Laurent
A1 Stefan Momma
A1 Ionita Ghiran
A1 Saumya Das
YR 2019
UL http://biorxiv.org/content/early/2019/05/02/624841.abstract
AB Extracellular vesicles (EV) mediate intercellular signaling by transferring their cargo to recipient cells. Red blood cell (RBC)-derived EVs constitute a significant proportion of circulating EVs and have been implicated in regulating immune responses. Here, we describe a transgenic mouse model for fluorescent-based mapping of RBC-EV target cells based on the functional transfer of EV-contained Cre-recombinase to target cells. In a murine model of ischemic heart failure, we detect an increase in RBC-EV-targeted cardiomyocytes in the hearts and microglial cells in the brains. Cells targeted by RBC-EVs present an enrichment of genes implicated in cell proliferation and metabolism pathways compared to non-recombined (non-targeted) cells. Cardiomyocytes targeted by RBC-EVs are more likely to demonstrate cellular markers of DNA synthesis and proliferation, suggesting functional significance of EV-mediated signaling. In conclusion, we leverage our mouse model for mapping of RBC-EV targets in murine ischemic heart failure to demonstrate quantitative and qualitative changes in RBC-EV recipients.