RESUMO
AIMS: Glycogen synthase kinase-3ß (GSK-3ß) and mitochondrial permeability transition pore (mPTP) play an important role in myocardial ischemia-reperfusion injury. The aim of this study was to investigate whether postconditioning with rosuvastatin is able to reduce myocardial ischemia-reperfusion injury and clarify the potential mechanisms. METHODS: Isolated rat hearts underwent 30 minutes of ischemia and 60 minutes of reperfusion in the presence or absence of rosuvastatin (1-50 nmol/L). The activity of signaling pathway was determined by Western blot analysis, and Ca2+ -induced mPTP opening was assessed by the use of a potentiometric method. RESULTS: Rosuvastatin significantly reduced myocardial infarct size and improved cardiac function at 5 and 10 nmol/L. Protection disappeared at higher concentration and reverted to increased damage at 50 nmol/L. At 5 nmol/L, rosuvastatin increased the phosphorylation of protein kinase B (Akt) and GSK-3ß, concomitant with a higher Ca2+ load required to open the mPTP. Rosuvastatin postconditioning also significantly increased superoxide dismutase activity and reduced malondialdehyde and radical oxygen species level. LY294002, phosphatidylinositol-3-kinase (PI3K) inhibitors, abolished these protective effects of rosuvastatin postconditioning. CONCLUSION: Rosuvastatin prevents myocardial ischemia-reperfusion injury by inducing phosphorylation of PI3K-Akt and GSK-3ß, preventing oxidative stress and subsequent inhibition of mPTP opening.
