Osteopontin protects against cardiac ischemia-reperfusion injury through late preconditioning.
Osteopontin (OPN) has been considered as a proinflammatory cytokine. A protective role for OPN in ischemic injury was demonstrated recently. Because proinflammatory cytokines play an important role in induction of late preconditioning, we deduce that OPN may induce late preconditioning in myocardium. Fifty consecutive patients scheduled for mitral valve replacement (MVR) were investigated. Osteopontin and high-sensitivity C-reactive protein levels in plasma before surgery were determined. Nuclear factor kappa B and signal transducer and activator of transcription 3 (STAT3), two main transcription factors involved in late preconditioning, were investigated by electrophoretic mobility shift assay. The effector proteins in late preconditioning, including inducible nitric oxide synthase and cyclooxygenase-2, were evaluated by immunoblotting. Cardioprotective effects were assessed by creatine kinase MB (CK-MB) and cardiac troponin T (cTnT) leakage postoperatively. The protective effects of OPN on neonatal cardiomyocytes against anoxia-reoxygenation-induced injury were also tested. The protein synthesis inhibitor cycloheximide (CH) was used in this model to test if new protein synthesis was necessary for its cardioprotective effects. There was no perioperative death in the groups. We found that patients with higher plasma OPN levels (167 +/- 35 ng/ml vs 63 +/- 13 ng/ml) had more activated extent of transcription factors, higher expression of effector proteins, and better cardioprotective effects, assessed by CK-MB and cTnT. An in vitro experiment also revealed that OPN had a cardioprotective effect 24 h after pretreatment. However, the protective effect was blocked by the protein synthesis inhibitor CH. Osteopontin can protect against cardiac ischemia-reperfusion injury through late preconditioning.
Wang
Yongyi
Y
Department of Cardiovascular Surgery, RenJi Hospital of Shanghai Jiaotong University, Shanghai, PR China.
Chen
Baofu
B
Shen
Dafu
D
Xue
Song
S