Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function
Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function
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DOI：
10.1073/pnas.161120198
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发表时间：
2001-08-14
影响因子：
11.1
通讯作者：
Croce, CM
中科院分区：
文献类型：
--
作者：
Condorelli, G;Roncarati, R;Croce, CM
据报道，促凋亡基因在心力衰竭和心肌梗塞中上调。为了确定 caspase 基因是否会影响心脏功能，我们培育了一只转基因小鼠。使用α-肌球蛋白重链的大鼠启动子诱导心脏组织特异性过度表达促凋亡基因Caspase3，该模型可能代表研究新分子和抗凋亡治疗策略的独特工具。心脏特异性 Caspase3 表达诱导短暂的心功能抑制以及异常的核和肌原纤维超微结构损伤。当遭受心肌缺血再灌注损伤时，Caspase3 转基因小鼠表现出梗塞面积增加和明显的死亡易感性。在这份报告中，我们记录了促凋亡基因 caspase3 对心肌收缩力的一个意想不到的特性。尽管诱导超微结构损伤，Caspase3 不会引发心肌细胞完全凋亡反应。我们还认为 Caspase3 参与确定缺血再灌注损伤后心肌梗塞的大小，因为其心肌细胞特异性过度表达会增加梗塞的大小。
Up-regulation of proapoptotic genes has been reported in heart failure and myocardial infarction. To determine whether caspase genes can affect cardiac function, a transgenic mouse was generated. Cardiac tissue-specific overexpression of the proapoptotic gene Caspase3 was induced by using the rat promoter of alpha -myosin heavy chain, a model that may represent a unique tool for investigating new molecules and antiapoptotic therapeutic strategies. Cardiac-specific Caspase3 expression induced transient depression of cardiac function and abnormal nuclear and myofibrillar ultrastructural damage. When subjected to myocardial ischemia-reperfusion injury, Caspase3 transgenic mice showed increased infarct size and a pronounced susceptibility to die. in this report, we document an unexpected property of the proapoptotic gene caspase3 on cardiac contractility. Despite inducing ultrastructural damage, Caspase3 does not trigger a full apoptotic response in the cardiomyocyte. We also implicate Caspase3 in determining myocardial infarct size after ischemia-reperfusion injury, because its cardiomyocyte-specific overexpression increases infarct size.