Cardiac-specific overexpression of Caspase3 in mice significantly depressed left ventricular fractional shortening at 9 weeks (29.9% vs 36.9%) and increased infarct size and mortality following ischemia-reperfusion injury.
Does cardiac-specific overexpression of Caspase3 increase infarct size and depress cardiac function in mice?
Cardiac-specific overexpression of Caspase3 in mice transiently depresses cardiac function and exacerbates myocardial damage and mortality following ischemia-reperfusion injury.
Absolute Event Rate: 29.9% vs 36.9%
p-value: p=<0.03
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.
Condorelli et al. (2001) studied Myocardial ischemia-reperfusion injury. Heart-targeted overexpression of Caspase3 vs. Wild-type littermates was evaluated on Left ventricular percent fractional shortening (%FS) at 9 weeks (p=<0.03). Cardiac-specific overexpression of Caspase3 in mice significantly depressed left ventricular fractional shortening at 9 weeks (29.9% vs 36.9%) and increased infarct size and mortality following ischemia-reperfusion injury.