Lipopolysaccharide pretreatment attenuates myocardial infarct size: A possible mechanism involving heat shock protein 70-inhibitory κBα complex and attenuation of nuclear factor κB

Abstract

Objective: Lipopolysaccharide pretreatment is known to reduce myocardial infarct size, but the mechanism has not been elucidated. We hypothesized that heat shock protein 70, induced by lipopolysaccharide pretreatment, formed complexes with inhibitory κBα, thereby inhibiting degradation and attenuating activation of nuclear factor κB and cellular injury in rat myocardium. Methods: Fifteen Sprague-Dawley rats were given saline solution (control group) or lipopolysaccharide. After 48 hours, 5 hearts in each group were excised without ischemia for examination of heat shock protein 70 and inhibitory κBα levels and detection of heat shock protein 70-inhibitory κBα complexes. Myocardium from the remaining 10 rats in each group was exposed to 30 minutes of ischemia and 30 minutes of reperfusion (n = 5) to evaluate nuclear factor κB activity or to 24 hours of reperfusion (n = 5) to evaluate infarct size. Results: Infarct size was reduced in the lipopolysaccharide group (P <.05). Nuclear factor κB was activated in the control ischemia group and attenuated in the lipopolysaccharide group (P <.05). Heat shock protein 70 levels were increased in the lipopolysaccharide group (P <.05), but inhibitory κBα levels were similar in both groups. Heat shock protein 70-inhibitory κBα complexes were detected only in the lipopolysaccharide group. Colocalization of the 2 proteins was observed in the lipopolysaccharide group. Conclusions: Heat shock protein 70, induced by lipopolysaccharide pretreatment, forms complexes with inhibitory κBα and attenuates activation of nuclear factor κB and myocardial infarct size. Our results suggest that attenuation of nuclear factor κB through a mechanism forming heat shock protein 70-inhibitory κBα complexes might protect the myocardium from ischemia-reperfusion injury.J Thorac Cardiovasc Surg 2002;124:933-41