Blocking the MyD88-dependent pathway protects the myocardium from ischemia/reperfusion injury in rat hearts

We examined whether blocking the MyD88 mediated pathway could protect myocardium from ischemia/reperfusion (I/R) injury by transfecting Ad5-dnMyD88 into the myocardium of rats (n = 8) 3 days before the hearts were subjected to ischemia (45 min) and reperfusion (4 h). Ad5-GFP served as control (n = 8). One group of rats was (n = 8) subjected to I/R without transfection. Transfection of Ad5-dnMyD88 significantly reduced infarct size by 53.6% compared with the I/R group (15.1 +/- 3.02 vs 32.5 +/- 2.59) while transfection of Ad5-GFP did not affect I/R induced myocardial injury (35.4 +/- 2.59 vs 32.5 +/- 2.59). Transfection of Ad5-dnMyM significantly inhibited I/R-enhanced NF kappa B activity by 50% and increased the levels of phospho-Akt by 35.6% and BCL-2 by 81%, respectively. Cardiac myocyte apoptosis after I/R was significantly reduced by 59% in the Ad5-dnMyD88 group. The results demonstrate that both inhibition of the NF kappa B activation pathway and activation of the Akt signaling pathway may be responsible for the protective effect of transfection of dominant negative MyD88. (c) 2005 Elsevier Inc. All rights reserved.