Red blood cell-derived extracellular vesicles mediate intercellular communication in ischemic heart failure

Das, A.; Valkov, N.; Salvador, A. M.; Kur, I.; Ziegler, O.; Yeri, A.; Garcia, F. C.; Lu, S.; Khamesra, A.; Xiao, C.; Rodosthenous, R.; Li, G.; Srinivasan, S.; Toxavidis, V.; Tigges, J.; Laurent, L. C.; Momma, S.; Ghiran, I.; Das, S.

doi:10.1101/624841

bioRxiv · 10.1101/624841

Red blood cell-derived extracellular vesicles mediate intercellular communication in ischemic heart failure

Das, A.·Valkov, N.·Salvador, A. M.·Kur, I.·Ziegler, O.·Yeri, A.·Garcia, F. C.·Lu, S.·Khamesra, A.·Xiao, C.·Rodosthenous, R.·Li, G.·Srinivasan, S.·Toxavidis, V.·Tigges, J.·Laurent, L. C.·Momma, S.·Ghiran, I.·Das, S.

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Abstract

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.

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Das, A., Valkov, N., Salvador, A. M., Kur, I., Ziegler, O., Yeri, A., Garcia, F. C., Lu, S., Khamesra, A., Xiao, C., Rodosthenous, R., Li, G., Srinivasan, S., Toxavidis, V., Tigges, J., Laurent, L. C., Momma, S., Ghiran, I., Das, S.. 2019-05-02. Red blood cell-derived extracellular vesicles mediate intercellular communication in ischemic heart failure. https://doi.org/10.1101/624841

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