Source:http://linkedlifedata.com/resource/pubmed/id/14615291
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
2004-1-12
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| pubmed:abstractText |
Cardiovascular disease is the leading cause of mortality and morbidity within the industrialized nations of the world, with coronary heart disease (CHD) accounting for as much as 66% of these deaths. Acute myocardial infarction is a typical sequelae associated with long-standing coronary heart disease resulting in large scale loss of ventricular myocardium through both apoptotic and necrotic cell death. In this study, we investigated the role that the calcium calmodulin-activated protein phosphatase calcineurin (PP2B) plays in modulating cardiac apoptosis after acute ischemia-reperfusion injury to the heart. Calcineurin Abeta gene-targeted mice showed a greater loss of viable myocardium, enhanced DNA laddering and TUNEL, and a greater loss in functional performance compared with strain-matched wild-type control mice after ischemia-reperfusion injury. RNA expression profiling was performed to uncover potential mechanisms associated with this loss of cardioprotection. Interestingly, calcineurin Abeta-/- hearts were characterized by a generalized downregulation in gene expression representing approximately 6% of all genes surveyed. Consistent with this observation, nuclear factor of activated T cells (NFAT)-luciferase reporter transgenic mice showed reduced expression in calcineurin Abeta-/- hearts at baseline and after ischemia-reperfusion injury. Finally, expression of an activated NFAT mutant protected cardiac myocytes from apoptotic stimuli, whereas directed inhibition of NFAT augmented cell death. These results represent the first genetic loss-of-function data showing a prosurvival role for calcineurin-NFAT signaling in the heart.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcineurin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
1524-4571
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| pubmed:author |
pubmed-author:AronowBruce JBJ,
pubmed-author:BuenoOrlando FOF,
pubmed-author:DaiYan-ShanYS,
pubmed-author:DoevendansPieter APA,
pubmed-author:GlascockBetty JBJ,
pubmed-author:HewettTimothy ETE,
pubmed-author:KaiserRobert ARA,
pubmed-author:KimballThomas RTR,
pubmed-author:KlevitskyRaisaR,
pubmed-author:LipsDaniel JDJ,
pubmed-author:MolkentinJeffery DJD,
pubmed-author:WilkinsBenjamin JBJ
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| pubmed:issnType |
Electronic
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| pubmed:day |
9
|
| pubmed:volume |
94
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
91-9
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:14615291-Animals,
pubmed-meshheading:14615291-Apoptosis,
pubmed-meshheading:14615291-Calcineurin,
pubmed-meshheading:14615291-Cell Survival,
pubmed-meshheading:14615291-Cells, Cultured,
pubmed-meshheading:14615291-DNA-Binding Proteins,
pubmed-meshheading:14615291-Gene Expression Profiling,
pubmed-meshheading:14615291-Gene Targeting,
pubmed-meshheading:14615291-Heart,
pubmed-meshheading:14615291-Mice,
pubmed-meshheading:14615291-Mice, Knockout,
pubmed-meshheading:14615291-Myocardial Infarction,
pubmed-meshheading:14615291-Myocardial Reperfusion Injury,
pubmed-meshheading:14615291-Myocardium,
pubmed-meshheading:14615291-Myocytes, Cardiac,
pubmed-meshheading:14615291-NFATC Transcription Factors,
pubmed-meshheading:14615291-Nuclear Proteins,
pubmed-meshheading:14615291-Transcription Factors
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| pubmed:year |
2004
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| pubmed:articleTitle |
Calcineurin Abeta gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction.
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| pubmed:affiliation |
Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|