Irisin plays a pivotal role to protect the heart against ischemia and reperfusion injury

Abstract

Irisin, a newly identified hormone, is critical to modulating body metabolism, thermogenesis and reducing oxidative stresses. 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 (100mg/kg) or vehicle for 30 minutes to elicit preconditioning. The isolated hearts were subjected to 30 min ischemia followed by 30 min reperfusion. Left ventricular function was measured and infarction size were determined using by tetrazolium staining. Western blot was employed to determine myocardial SOD-1, active-caspase 3, annexin V, p38 and phospho-p38. 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-1 and p38 phosphorylation, but suppressed levels of active-caspase 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.

FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT

“…Farzaneh et al found that the mRNA level of Fndc5 was increased during the process of cardiac differentiation, and overexpression of FNDC5 significantly increased whereas Fndc5 deficiency decreased cardiomyocyte differentiation rate of mouse embryonic stem cells [50][51][52]. In addition, several researches have proved that FNDC5/Irisin played a pivotal role in protecting the heart against ischemia/reperfusion injury and could be a potentially candidate marker for myocardial infarction [23,53,54]. Irisin supplementation could also attenuate collagen deposition and ventricular function impairment in diabetic hearts [55].…”

“…Liu et al found that Fndc5 deficiency aggravated whereas FNDC5 overexpression prevented obesity-related hyperlipemia, hepatic lipid accumulation, and impaired fatty acid oxidation and autophagy in the liver [20]. Except for the beneficial role in metabolic disorders, recent studies also implicated that FNDC5/Irisin was involved in regulating various cardiovascular diseases, such as atherosclerosis, hypertension, myocardial ischemia/reperfusion injury, and cardiac hypertrophy [21][22][23][24]. Besides, numerous researches verified that FNDC5 overexpression or irisin supplementation could preserve mitochondrial function and attenuate oxidative damage as well as cell apoptosis [25,26].…”

Measuring myokines with cardiovascular functions: pre-analytical variables affecting the analytical output

“…In myocardium, it is induced by ischemia and it protects against ischemia and reperfusion heart injury, by improving post-ischemic ventricular function, coronary effluent recovery, and reducing the infarct size. Furthermore, irisin decreases the expression of apoptotic proteins including active caspase-3, cleaved PARP, and annexin V and increases p38 phosphorylation and SOD-1 expression in the post-ischemic myocardium (52).…”

Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients

“…Besides that, increased circulating irisin levels were also demonstrated to be associated with MACE in coronary artery disease patients after percutaneous coronary interventions. Of note, the protective effects of irisin in cardiovascular diseases have consistently been reported [26-30]. Thus, the elevated circulating irisin levels in patients with risk for cardiovascular diseases or MACE have been considered as a state of irisin-resistance.…”