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01-07-2017 | Original Contribution

Exercise-induced circulating extracellular vesicles protect against cardiac ischemia–reperfusion injury

Authors: Yihua Bei, Tianzhao Xu, Dongchao Lv, Pujiao Yu, Jiahong Xu, Lin Che, Avash Das, John Tigges, Vassilios Toxavidis, Ionita Ghiran, Ravi Shah, Yongqin Li, Yuhui Zhang, Saumya Das, Junjie Xiao

Published in: Basic Research in Cardiology | Issue 4/2017

Abstract

Extracellular vesicles (EVs) serve an important function as mediators of intercellular communication. Exercise is protective for the heart, although the signaling mechanisms that mediate this cardioprotection have not been fully elucidated. Here using nano-flow cytometry, we found a rapid increase in plasma EVs in human subjects undergoing exercise stress testing. We subsequently identified that serum EVs were increased by ~1.85-fold in mice after 3-week swimming. Intramyocardial injection of equivalent quantities of EVs from exercised mice and non-exercised controls provided similar protective effects against acute ischemia/reperfusion (I/R) injury in mice. However, injection of exercise-induced EVs in a quantity equivalent to the increase seen with exercise (1.85 swim group) significantly enhanced the protective effect. Similarly, treatment with exercise-induced increased EVs provided additional anti-apoptotic effect in H₂O₂-treated H9C2 cardiomyocytes mediated by the activation of ERK1/2 and HSP27 signaling. Finally, by treating H9C2 cells with insulin-like growth factor-1 to mimic exercise stimulus in vitro, we found an increased release of EVs from cardiomyocytes associated with ALIX and RAB35 activation. Collectively, our results show that exercise-induced increase in circulating EVs enhances the protective effects of endogenous EVs against cardiac I/R injury. Exercise-derived EVs might serve as a potent therapy for myocardial injury in the future.

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Title: Exercise-induced circulating extracellular vesicles protect against cardiac ischemia–reperfusion injury
Authors: Yihua Bei
Tianzhao Xu
Dongchao Lv
Pujiao Yu
Jiahong Xu
Lin Che
Avash Das
John Tigges
Vassilios Toxavidis
Ionita Ghiran
Ravi Shah
Yongqin Li
Yuhui Zhang
Saumya Das
Junjie Xiao
Publication date: 01-07-2017
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 4/2017
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-017-0628-z

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