This study aimed to investigate the role of PPARγ and underlying mechanisms in myocardial ischemia/reperfusion injury (IRI). IRI was surgically induced in mice and neonatal rat cardiomyocytes (NRCM) were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R). Quantitative genetic analysis and western blotting were performed to assess mRNA and protein levels, respectively, of PPARγ, as well as of different inflammatory, fibrosis, and apoptosis markers in cells and tissues. PPARγ was overexpressed in the heart of mice and NRCMs by viral transfection. Apoptosis and fibrosis were detected by TUNEL and Masson's trichrome staining, respectively. Enzyme-linked immunosorbent assay was performed to detect M1 and M2 macrophage-related inflammatory factors present in mouse sera. PPARγ overexpression significantly inhibited OGD/R- and IRI-induced cardiomyocyte apoptosis and fibrosis in vitro and in vivo. Moreover, PPARγ overexpression inhibited IRI-induced secretion of M1-related proinflammatory factors, whereas it supported the secretion of M2-related anti-inflammatory factors. Notably, these events were found to be mediated by the JAK/STAT pathway. In conclusion, PPARγ regulates macrophage polarization upon IRI via the JAK/STAT pathway, which will in turn prevent myocardial apoptosis and fibrosis. Hence, PPARγ may represent a valuable target for myocardial IRI treatment.
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