Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function

Gianluigi Condorelli, Roberta Roncarati, John Ross, Angela Pisani, Giorgio Stassi, Matilde Todaro, Stephen Trocha, Alessandra Drusco, Yusu Gu, Matteo A. Russo, Giacomo Frati, Steven P. Jones, David J. Lefer, Claudio Napoli, Carlo M. Croce

Research output: Contribution to journalArticle

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 α-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.

Original languageEnglish
Pages (from-to)9977-9982
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number17
DOIs
Publication statusPublished - Aug 14 2001

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Reperfusion Injury
Cardiac Myocytes
Transgenic Mice
Genes
Myocardial Infarction
Myocardial Reperfusion Injury
Myosin Heavy Chains
Caspases
Myocardial Ischemia
Up-Regulation
Heart Failure
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function. / Condorelli, Gianluigi; Roncarati, Roberta; Ross, John; Pisani, Angela; Stassi, Giorgio; Todaro, Matilde; Trocha, Stephen; Drusco, Alessandra; Gu, Yusu; Russo, Matteo A.; Frati, Giacomo; Jones, Steven P.; Lefer, David J.; Napoli, Claudio; Croce, Carlo M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 17, 14.08.2001, p. 9977-9982.

Research output: Contribution to journalArticle

Condorelli, Gianluigi ; Roncarati, Roberta ; Ross, John ; Pisani, Angela ; Stassi, Giorgio ; Todaro, Matilde ; Trocha, Stephen ; Drusco, Alessandra ; Gu, Yusu ; Russo, Matteo A. ; Frati, Giacomo ; Jones, Steven P. ; Lefer, David J. ; Napoli, Claudio ; Croce, Carlo M. / Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 17. pp. 9977-9982.
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