Gene Transfer of Heat-Shock Protein 70 Reduces Infarct Size In Vivo After Ischemia/Reperfusion in the Rabbit Heart

Abstract

Background —Heat-shock protein 70 (HSP 70) plays a role in myocardial protection. No studies are available, however, to show that direct gene transfer of HSP 70 reduces myocardial infarction in vivo. Methods and Results —Rabbit hearts were injected with vehicle or Ad.HSP70 at 3 sites (1.5×10 9 pfu, 50 μL/site) in the left ventricle (LV). Four days later, hearts were removed, and expression of inducible (HSP 70) and constitutive (HSC 70) proteins was measured in the LV and right ventricle (RV). Subsets of 5 to 7 animals in the vehicle-, Ad.lacZ-, and Ad.HSP70-treated groups were subjected to 30 minutes of ischemia and 3 hours of reperfusion. Infarct size was measured by tetrazolium staining. Increased expression of HSP 70 was observed in LV injected with Ad.HSP70 compared with vehicle-treated hearts. HSP 70 was undetectable in RV, the noninjected region of the heart. The expression of HSC 70 remained unchanged in hearts treated with vehicle or Ad.HSP70. Infarct size (% risk area) decreased to 24.5±2.8 in Ad.HSP70-injected hearts compared with 41.9±2.8 and 42.7±2.5 in the vehicle- and Ad.LacZ-treated hearts ( P <0.01). The infarct size was not different between the vehicle- and Ad.LacZ-treated hearts ( P >0.05). The risk areas (% of LV) were not different among the 3 groups, ie, 50.1±5.2, 47.7±3.5, and 53.3±2.9 in vehicle-, Ad.lacZ-, and Ad.HSP70-treated groups ( P >0.05). Conclusions —Direct gene delivery of HSP 70 in vivo reduces the severity of ischemic injury in the heart.