Transfection of Heat-Shock Protein 70 Enhances Myocardial Tolerance to Ischemia: Evidence for a Role of HSP70 in Ischemia-Reperfusion Injury

The enhancement of myocardial tolerance mediated by heat-shock protein 70 (HSP70) can be utilized for further advancement in myocardial protection in clinical settings. Recently, we have developed a novel in vivo gene transfection method for the entire heart. We investigated the possibility of enhancing myocardial tolerance to ischemia-reperfusion injury by introducing the HSP70 gene into the whole heart by means of in vivo gene transfection with HVJ (Hemagglutinating virus of Japan)-liposome procedure. HVJ-liposome, either with the human HSP70 gene (H group; n = 5) or without the gene (C group; n = 5), was infused into rat hearts via the coronary arteries. The hearts obtained from nontreated rats (N group; n = 5) were also examined. Western blotting analysis clearly showed overexpression of HSP70 in the H group. Recovery rate of left ventricular developed pressure, rate-pressure product, and coronary flow after ischemia-reperfusion injury (37°C, 30 minutes) were significantly higher for the H group than for either the C or N group (p < 0.05). CK leakage for the first five minutes of reperfusion was lower in the H group than in the C and N groups (p < 0.05). HSP70 was overexpressed in rat hearts as a result of in vivo gene transfection with HVJ-liposome. Higher myocardial tolerance to ischemia-reperfusion injury was observed in the HSP70-overexpressing heart as compared to the control and even the nontreated hearts. Our results demonstrate the protective effect of gene-transfection-induced HSP70 against ischemia-reperfusion injury in the myocardium, suggesting the possibility of clinical application of gene therapy with HSP70 to ischemia-reperfusion injury.