Document Detail


Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function.
MedLine Citation:
PMID:  11493678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
G Condorelli; R Roncarati; J Ross; A Pisani; G Stassi; M Todaro; S Trocha; A Drusco; Y Gu; M A Russo; G Frati; S P Jones; D J Lefer; C Napoli; C M Croce
Related Documents :
23567658 - Fty720 postconditions isolated perfused heart by a mechanism independent of sphingosine...
20820108 - Drug-disease interaction: reduced verapamil response in isoproterenol-induced myocardia...
20966608 - Bay 11-7082, a nuclear factor-κb inhibitor, reduces inflammation and apoptosis in a ra...
22998368 - The pharmacokinetics and pharmacodynamics of valsartan in the post-myocardial infarctio...
24640518 - Strain imaging for evaluating response to thrombolytic therapy in pulmonary thromboembo...
20427988 - Heart failure: pathophysiology and clinical picture.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2001-08-07
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  98     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-15     Completed Date:  2001-09-20     Revised Date:  2013-04-17    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9977-82     Citation Subset:  IM    
Affiliation:
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107-5541, USA. gianluigi.condorelli@mail.tju.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / genetics
Caspase 3
Caspases / genetics,  physiology*
DNA Fragmentation
DNA, Complementary / genetics
Echocardiography
Gene Expression Regulation
Genetic Predisposition to Disease
Humans
Mice
Mice, Transgenic
Myocardial Infarction / enzymology*,  pathology,  ultrasonography
Myocardial Ischemia / enzymology,  pathology
Myocardial Reperfusion Injury / enzymology*,  pathology,  ultrasonography
Myocardium / enzymology*,  pathology
Organ Specificity
Phenotype
Recombinant Fusion Proteins / physiology
Ventricular Dysfunction, Left / enzymology*,  etiology
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/Recombinant Fusion Proteins; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Transgene analysis proves mRNA trans-splicing at the complex mod(mdg4) locus in Drosophila.
Next Document:  The yeast mutant vps5Delta affected in the recycling of Golgi membrane proteins displays an enhanced...