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 a-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.
Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function / G. L., Condorelli; R., Roncarati; Ross J., Jr; A., Pisani; G., Stassi; M., Todaro; S., Trocha; A., Drusco; Y., Gu; Russo, Matteo Antonio; Frati, Giacomo; S. P., Jones; D. J., Lefer; C., Napoli; C. M., Croce. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - STAMPA. - 98:17(2001), pp. 9977-9982. [10.1073/pnas.161120198]
Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function
RUSSO, Matteo Antonio;FRATI, GIACOMO;
2001
Abstract
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 a-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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.