6533b86cfe1ef96bd12c8c6c
RESEARCH PRODUCT
Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function
Matilde TodaroJohn RossStephen TrochaGiacomo FratiAngela PisaniDavid J. LeferMatteo Antonio RussoYusu GuRoberta RoncaratiClaudio NapoliSteven P. JonesCarlo M. CroceGiorgio StassiGianluigi CondorelliAlessandra Druscosubject
Genetically modified mouseCardiac function curveDNA ComplementaryTransgeneRecombinant Fusion ProteinsMyocardial InfarctionMyocardial IschemiaCaspase 3ApoptosisMice TransgenicMyocardial Reperfusion InjuryDNA FragmentationContractilityMiceVentricular Dysfunction LeftmedicineAnimalsHumansGenetic Predisposition to DiseaseMyocardial infarctionCaspaseMultidisciplinarybiologyCaspase 3MyocardiumBiological Sciencesmedicine.diseasePhenotypeGene Expression RegulationEchocardiographyOrgan SpecificityHeart failureCaspasesCancer researchbiology.proteincardiovascular systemdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2001-08-07 |