Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosis.
Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosis.
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DOI：
10.1152/ajpheart.00133.2002
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发表时间：
2002-08
期刊：
影响因子：
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通讯作者：
Sreesatya Raju Vulapalli;Zhongyi Chen;B. Chua;Tingchung Wang;C. Liang
中科院分区：
文献类型：
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作者：
Sreesatya Raju Vulapalli;Zhongyi Chen;B. Chua;Tingchung Wang;C. Liang
血红素加氧酶 (HO)-1 将血红素转化为胆红素、一氧化碳和铁。我们之前的工作表明 HO-1 在心力衰竭中具有心脏保护作用。为了测试 HO-1（热休克蛋白 32）是否可以预防缺血再灌注（I/R）后心肌细胞凋亡和心功能障碍，我们培育了在 α-肌球蛋白重链启动子控制下在心脏中过表达 HO-1 的转基因小鼠。 HO-1 转录物和蛋白质仅在心脏中显着增加。在离体心脏制备中，我们观察到与非转基因对照相比，转基因心脏缺血后再灌注期间功能恢复增强。还通过冠状动脉结扎和再灌注对完整动物进行 I/R 损伤，以评估 HO-1 过表达对心脏细胞凋亡的保护作用。与非转基因小鼠相比，HO-1 过表达减少了心脏细胞凋亡，这一点可以通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记阳性或原位寡核苷酸连接阳性心肌细胞减少来证明。我们的结果表明，HO-1 的心脏选择性过度表达在小鼠心肌缺血再灌注后发挥心脏保护作用，并且这种作用可能是通过 HO-1 的抗凋亡作用介导的。
Heme oxygenase (HO)-1 converts heme to bilirubin, carbon monoxide, and iron. Our prior work has suggested a cardioprotective role for HO-1 in heart failure. To test whether HO-1 (heat shock protein 32) prevents cardiomyocyte apoptosis and cardiac dysfunction after ischemia-reperfusion (I/R), we generated transgenic mice overexpressing HO-1 in the heart under the control of the alpha-myosin heavy chain promoter. HO-1 transcript and protein increased markedly in the heart only. In an isolated heart preparation, we observed an enhanced functional recovery during reperfusion after ischemia in the transgenic hearts compared with nontransgenic controls. I/R injury was also performed in intact animals by coronary ligation and reperfusion to assess the protective role of HO-1 overexpression on heart apoptosis. HO-1 overexpression reduced cardiac apoptosis, as evidenced by fewer terminal deoxynucleodidyl transferase-mediated dUTP nick-end labeling-positive or in situ oligo ligation-positive myocytes, compared with nontransgenic mice. Our results indicate that cardioselective overexpression of HO-1 exerts a cardioprotective effect after myocardial I/R in mice, and this effect is probably mediated via an antiapoptotic action of HO-1.