Nuclear Factor-κB Protects the Adult Cardiac Myocyte Against Ischemia-Induced Apoptosis in a Murine Model of Acute Myocardial Infarction

Abstract

Background— Previous studies have shown that tumor necrosis factor (TNF) confers cytoprotective responses in cardiac myocytes. However, the mechanisms for the cytoprotective effects of TNF remain unknown. Given that TNF signals through nuclear factor κB (NF-κB) and given that NF-κB mediates cytoprotective responses, we asked whether NF-κB activation conferred cytoprotective responses in acute myocardial ischemia/infarction. Methods and Results— We examined infarct size and the prevalence of apoptosis in transgenic mice harboring cardiac-restricted expression of a mutated IκBα protein (IκBαΔN) that prevents nuclear translocation of NF-κB in cardiac myocytes. Triphenyltetrazolium chloride staining showed that infarct size was ≈50% greater ( P P Conclusions— Transgenic mice with a defect in activation of NF-κB have increased susceptibility to tissue injury after acute left anterior descending occlusion. These studies suggest that the cytoprotective effects of NF-κB are mediated, at least in part, by Bcl-2 or c-IAP1.