Abstract 17072: Disruption of mTORC2 Integrity Underlies Increased Myocardial Susceptibility to Ischemia/reperfusion Injury in Chronic Renal Failure

Objective: Chronic renal failure (CRF) worsens prognosis after myocardial infarction, but its impact on myocardial injury remains unclear. We recently found that mTORC2, a kinase complex promoting phosphorylation of Akt at Ser473, plays a pivotal role in cardioprotection. Here, we tested the hypothesis that CRF increases myocardial susceptibility to ischemia/reperfusion injury by disrupting mTORC2 activation. Methods and results: Rats underwent 5/6 nephrectomy (subtotal nephrectomy, SNx) or a sham operation (Sham). Levels of serum creatinine at 4 weeks after the operation were higher in SNx (n=7) than in Sham (n=8) (0.72±0.05 vs. 0.33±0.05 mg/dl, p Conclusion: Taken together with previous reports that CRF up-regulates oxidative stress level in the myocardium, the present results suggest that oxidative stress-mediated disruption of mTOC2 integrity, leading to impaired phosphorylation of Akt at Ser473 upon reperfusion, underlies the increased myocardial susceptibility to ischemia/reperfusion injury in CRF.