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However, whether irisin protects the heart against myocardial ischemia and reperfusion (I\/R) injury remains unknown. In this study, we determine the effect of irisin on myocardial I\/R injury in the Langendorff perfused heart and cultured myocytes. Adult C57\/BL6 mice were treated with irisin (100\u2009mg\/kg) or vehicle for 30\u2009min to elicit preconditioning. The isolated hearts were subjected to 30\u2009min ischemia followed by 30\u2009min reperfusion. Left ventricular function was measured and infarction size were determined using by tetrazolium staining. Western blot was employed to determine myocardial SOD\u20101, active\u2010caspase 3, annexin V, p38, and phospho\u2010p38. H9c2 cardiomyoblasts were exposed to hypoxia and reoxygenation for assessment of the effects of irisin on mitochondrial respiration and mitochondrial permeability transition pore (mPTP). Irisin treatment produced remarkable improvements in ventricular functional recovery, as evident by the increase in RPP and attenuation in LVEDP. As compared to the vehicle treatment, irisin resulted in a marked reduction of myocardial infarct size. Notably, irisin treatment increased SOD\u20101 and p38 phosphorylation, but suppressed levels of active\u2010caspase 3, cleaved PARP, and annexin V. In cardiomyoblasts exposed to hypoxia\/reoxygenation, irisin treatment significantly attenuated hypoxia\/reoxygenation (H\/R), as indicated by the reduction of lactate dehydrogenase (LDH) leakage and apoptotic cardiomyocytes. Furthermore, irisin treatments suppressed the opening of mPTP, mitochondrial swelling, and protected mitochondria function. Our results indicate that irisin serves as a novel approach to eliciting cardioprotection, which is associated with the improvement of mitochondrial function.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25857","type":"journal-article","created":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T12:22:44Z","timestamp":1486642964000},"page":"3775-3785","source":"Crossref","is-referenced-by-count":123,"title":["Irisin plays a pivotal role to protect the heart against ischemia and reperfusion injury"],"prefix":"10.1002","volume":"232","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Surgery Boston University Medical School Roger Williams Medical Center Providence Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Tina","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Surgery Boston University Medical School Roger Williams Medical Center Providence Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Luoyang Central Hospital affiliated to Zhengzhou University Luoyang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja M","family":"Dubielecka","sequence":"additional","affiliation":[{"name":"Department of Medicine Alpert Medical School Brown University Providence Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Surgery Boston University Medical School Roger Williams Medical Center Providence Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiro","family":"Yano","sequence":"additional","affiliation":[{"name":"Women and Infants Hospital Brown University Providence Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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