Anti-Ischemic Effect of Leptin in the Isolated Rat Heart Subjected to Global Ischemia-Reperfusion: Role of Cardiac-Specific miRNAs

Abstract

Background: Leptin is an obesity-associated adipokine that has been implicated in cardiac protection against ischemia-reperfusion injury (IRI). In this study, concentration-dependent effects of leptin on myocardial IRI were investigated in the isolated rat heart. In addition, we analyzed myocardial miRNAs expression in order to investigate their potential involvement in leptin-mediated cardioprotection. Methods: The effect of leptin on IRI was examined in Langendorff-perfused rat hearts preconditioned with two leptin concentrations (1.0 nM and 3.1 nM) for 60 min. The hearts were subjected to 30 min global ischemia and 120 min reperfusion with buffer containing leptin in the respective concentration. Heart function and arrhythmia incidence were analyzed. Infarct size was assessed histochemically. Expression of miRNA-144, -208a, -378, and -499 was analyzed in the ventricular myocardium using RT-PCR. Results: The addition of 1.0 nM leptin to the buffer exerted an infarct-limiting effect, preserved post-ischemic ventricular function, and prevented reperfusion arrhythmia compared to 3.1 nM leptin. Myocardial expression of miRNA-208a was decreased after heart exposure to 1.0 nM leptin and significantly elevated in the hearts perfused with leptin at 3.1 nM. Conclusion: Acute administration of leptin at low dose (1.0 nM) results in cardiac protection against IRI. This effect is associated with reduced myocardial expression of miRNA-208a.