Objectives Evidence exists that the increase of TNFα is associated with reperfusion injury in patients with myocardial infarction after PCI. Adiponectin (APN) is anti-infl ammatory and cardioprotective protein suppressed by TNFα, and is signifi cantly reduced during MI/R. Whether neutralising TNFα protects against MI/R injury through upregulation of APN level has not been previously investigated. Methods and Results Adult male C57 mice were subjected to 30 min MI followed by 3h or 24h

more »

... n or sham MI/R for this study. Etanercept, a TNFα neutralising drug for treating rheumatoid arthritis in clinic, was intraperitoneally injected 10 min before reperfusion. Etanercept administration ameliorated MI/R injury evidenced by increased cardiac function (1 day, 7 day, 14 day p<0.05 vs vehicle), reduced infarct size (p <0.05 vs vehicle) and apoptosis (p<0.01 vs vehicle). Etanercept signifi cantly increased plasma APN concentration at 3 h, 8 h, 1 day and 3 days after reperfusion, respectively (all p<0.05 vs vehicle) and pAMPK/AMPK ratio at 3 h in myocardium (p<0.05 vs vehicle). To further investigate whether Etanercept attenuated MI/R injury is related to the APN signalling, additional experiments were performed. Firstly, the siRNA was used to knockdown (KD) the APN receptor 1 & receptor 2 (APN-R1&2) by intramyocardial injection 48 h before MI/R in vivo. APN receptor knockdown attenuated the cardioprotective effect induced by Etanercept supported by decreased infarct size (10% decrease in KD+Etanercept vs 25% decrease in WT+Etanercept), apoptosis (caspase-3 activity 21% vs 35% reduction) and lower pAMPK/AMPK ratio. second, the ob/ob mice, which APN signalling is impaired, were subjected to the MI/R following the same procedure. The cardioprotective effect of Etanercept was attenuated in the ob/ob mice compared with the wild type mice as well.