Rosuvastatin postconditioning protects isolated hearts against ischemia–reperfusion injury: The role of radical oxygen species, PI3K–Akt–GSK‐3β pathway, and mitochondrial permeability transition pore

Summary Aims Glycogen synthase kinase‐3β ( GSK ‐3β) 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 Ca 2+ ‐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 ‐3β, concomitant with a higher Ca 2+ load required to open the mPTP . Rosuvastatin postconditioning also significantly increased superoxide dismutase activity and reduced malondialdehyde and radical oxygen species level. LY 294002, phosphatidylinositol‐3‐kinase ( PI 3K) inhibitors, abolished these protective effects of rosuvastatin postconditioning. Conclusion Rosuvastatin prevents myocardial ischemia–reperfusion injury by inducing phosphorylation of PI 3K–Akt and GSK ‐3β, preventing oxidative stress and subsequent inhibition of mPTP opening.