Reduction in myocardial apoptosis associated with overexpression of heat shock protein 70
Reduction in myocardial apoptosis associated with overexpression of heat shock protein 70
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DOI：
10.1007/s003950070039
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发表时间：
2000-10-01
影响因子：
9.5
通讯作者：
Matsuda, H
中科院分区：
文献类型：
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作者：
Suzuki, K;Sawa, Y;Matsuda, H
缺血再灌注诱导心肌细胞凋亡。热休克蛋白70 （HSP70）增强心肌耐受性。因此，我们推测HSP70可能在心肌细胞凋亡的衰减中起作用。为了阐明这一目的，采用冠状动脉内灌注日本脂质体血凝病毒基因转染制备了hsp70过表达和对照转染的大鼠心脏。体内实验两组心脏均进行全身缺血后原位再灌注。在hsp70转染组中，自发心跳恢复时间较短（hsp70转染组比对照组；46.7 +/- 4.6 vs 67.5 +/- 7.0 s, p = 0.033），血清CPK水平较低（415 +/- 27 vs 533 +/- 36 IU, p = 0.027）。hsp70转染组缺血再灌注后心肌细胞缺口末端标记阳性比例也较低（17.5 +/- 4.9 vs 40.0 +/- 5.1%, p = 0.010）。体外实验取两组心脏分离的心肌细胞（与体内实验分开制备）进行缺氧复氧处理。流式细胞术检测显示亚g (1) DNA含量的细胞为凋亡细胞。缺氧复氧后，凋亡细胞占活细胞的百分比在对照组中增加更多（13.0 +/- 0.77 vs 21.9 +/- 1.18%, p < 0.0001）。综上所述，我们在体内和体外实验证明，HSP70过表达的心脏缺血再灌注后的细胞凋亡减少，提示HSP70可能与心肌细胞凋亡减少有关。
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.