Reduction in myocardial apoptosis associated with overexpression of heat shock protein 70

It is reported that ischemia-reperfusion induces apoptotic cell death in myocardium. It is also demonstrated that heat shock protein 70 (HSP70) enhances myocardial tolerance. Therefore, it is hypothesized that HSP70 may play a role in the attenuation of myocardial apoptosis. To elucidate this goal, HSP70-overexpressing and control-transfected rat hearts were prepared using gene transfection by intra-coronary infusion of the hemagglutinating virus of Japan-liposome. In vivo experiment Hearts of both groups were subjected to global ischemia, followed by reperfusion in situ. Shorter recovery time to spontaneous beating (HSP70-transfected vs control-transfected; 46.7 +/- 4.6 vs 67.5 +/- 7.0 s, p = 0.033) and lower serum CPK levels (415 +/- 27 vs 533 +/- 36 IU, p = 0.027) were observed in the HSP70-transfected group. The HSP70-transfected group also showed a lower percentage of cardiac myocytes positively stained by nick end labeling after ischemia-reperfusion (17.5 +/- 4.9 vs 40.0 +/- 5.1 %, p = 0.010). In vitro experiment Cardiac myocytes isolated from the hearts of both groups (prepared separately from the in vivo experiment) were subjected to hypoxia-reoxygenation. Flow cytometry was used to identify the cells that showed sub-G(1) DNA content as apoptotic cells. Apoptotic cells as a percentage of viable cells increased more in the control-transfected group after hypoxia-reoxygenation (13.0 +/- 0.77 vs 21.9 +/- 1.18 %, p < 0.0001). In conclusion, we demonstrated that apoptosis after ischemia-reperfusion was decreased in the HSP70-overexpressin heart in vivo and in vitro, leading to the suggestion that HSP70 could be associated with the reduction in myocardial apoptosis.