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-G1 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-overexpressing heart in vivo and in vitro, leading to the suggestion that HSP70 could be associated with the reduction in myocardial apoptosis.
Suzuki
K
K
First Department of Surgery, Osaka University Medical School, Suita, Japan.
Sawa
Y
Y
Kagisaki
K
K
Taketani
S
S
Ichikawa
H
H
Kaneda
Y
Y
Matsuda
H
H
D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018840:HSP70 Heat-Shock Proteins