Calcium Ionophore-Induced Extracellular Vesicles Mediate Cytoprotection against Simulated Ischemia/Reperfusion Injury in Cardiomyocyte-Derived Cell Lines by Inducing Heme Oxygenase 1

International Journal of Molecular Sciences

Monika Barteková¹  Anikó Görbe²  Szabolcs Hambalkó²  Zoltán Giricz²  Csilla Pelyhe²  CsillaT. Nagy²  Péter Ferdinandy²  Bence Kenyeres²  GáborB. Brenner²  Ágnes Kittel³  Duško Lainšček⁴  Mateja Manček-Keber⁴  Peter Pečan⁴  VanThai Ha⁴ 

[1] Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 84104 Bratislava, Slovakia;Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1085 Budapest, Hungary;Institute of Experimental Medicine, ELRN, 1083 Budapest, Hungary;National Institute of Chemistry, SI-1000 Ljubljana, Slovenia;

关键词: extracellular vesicles;    TLR4;    HO-1;    cardioprotection;    ischemia/reperfusion injury;   

DOI  :  10.3390/ijms21207687

来源: DOAJ

【 摘 要 】

Cardioprotection against ischemia/reperfusion injury is still an unmet clinical need. The transient activation of Toll-like receptors (TLRs) has been implicated in cardioprotection, which may be achieved by treatment with blood-derived extracellular vesicles (EVs). However, since the isolation of EVs from blood takes considerable effort, the aim of our study was to establish a cellular model from which cardioprotective EVs can be isolated in a well-reproducible manner. EV release was induced in HEK293 cells with calcium ionophore A23187. EVs were characterized and cytoprotection was assessed in H9c2 and AC16 cell lines. Cardioprotection afforded by EVs and its mechanism were investigated after 16 h simulated ischemia and 2 h reperfusion. The induction of HEK293 cells by calcium ionophore resulted in the release of heterogenous populations of EVs. In H9c2 and AC16 cells, stressEVs induced the downstream signaling of TLR4 and heme oxygenase 1 (HO-1) expression in H9c2 cells. StressEVs decreased necrosis due to simulated ischemia/reperfusion injury in H9c2 and AC16 cells, which was independent of TLR4 induction, but not that of HO-1. Calcium ionophore-induced EVs exert cytoprotection by inducing HO-1 in a TLR4-independent manner.

【 授权许可】

Unknown