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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2004-12-3
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pubmed:abstractText |
Cardiac-restricted overexpression of the Ca2+-binding protein S100A1 has been shown to lead to increased myocardial contractile performance in vitro and in vivo. Since decreased cardiac expression of S100A1 is a characteristic of heart failure, we tested the hypothesis that S100A1 gene transfer could restore contractile function of failing myocardium. Adenoviral S100A1 gene delivery normalized S100A1 protein expression in a postinfarction rat heart failure model and reversed contractile dysfunction of failing myocardium in vivo and in vitro. S100A1 gene transfer to failing cardiomyocytes restored diminished intracellular Ca2+ transients and sarcoplasmic reticulum (SR) Ca2+ load mechanistically due to increased SR Ca2+ uptake and reduced SR Ca2+ leak. Moreover, S100A1 gene transfer decreased elevated intracellular Na+ concentrations to levels detected in nonfailing cardiomyocytes, reversed reactivated fetal gene expression, and restored energy supply in failing cardiomyocytes. Intracoronary adenovirus-mediated S100A1 gene delivery in vivo to the postinfarcted failing rat heart normalized myocardial contractile function and Ca2+ handling, which provided support in a physiological context for results found in myocytes. Thus, the present study demonstrates that restoration of S100A1 protein levels in failing myocardium by gene transfer may be a novel therapeutic strategy for the treatment of heart failure.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-10639159,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-11044432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-11717446,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-11805843,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-11850507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-11909974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-12392982,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-12618512,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-12619862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-12645002,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-12650866,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-12707260,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-12721284,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-12777394,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-12804600,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-12960148,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-14523037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-15079813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-3260516,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-3276520,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-8898862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-9298970,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-9482916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-9560262,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-9614121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15578088-9614485
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9738
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pubmed:author |
pubmed-author:BoerriesMelanieM,
pubmed-author:EckhartAndrea DAD,
pubmed-author:HeidtBeatrixB,
pubmed-author:JanssenPaul M LPM,
pubmed-author:KatusHugo AHA,
pubmed-author:KochWalter JWJ,
pubmed-author:LöfflerEvaE,
pubmed-author:MartiniJeffreyJ,
pubmed-author:MostPatrickP,
pubmed-author:PlegerSven TST,
pubmed-author:RemppisAndrewA,
pubmed-author:VölkersMirkoM,
pubmed-author:WeichenhanDieterD,
pubmed-author:WilliamsMatthew LML
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pubmed:issnType |
Print
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pubmed:volume |
114
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1550-63
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15578088-Adenoviridae,
pubmed-meshheading:15578088-Animals,
pubmed-meshheading:15578088-COS Cells,
pubmed-meshheading:15578088-Calcium,
pubmed-meshheading:15578088-Calcium-Binding Proteins,
pubmed-meshheading:15578088-Calcium-Transporting ATPases,
pubmed-meshheading:15578088-Cardiac Output, Low,
pubmed-meshheading:15578088-Cercopithecus aethiops,
pubmed-meshheading:15578088-Female,
pubmed-meshheading:15578088-Gene Expression Regulation, Developmental,
pubmed-meshheading:15578088-Gene Therapy,
pubmed-meshheading:15578088-Gene Transfer Techniques,
pubmed-meshheading:15578088-Genetic Vectors,
pubmed-meshheading:15578088-Heart,
pubmed-meshheading:15578088-Hemodynamics,
pubmed-meshheading:15578088-Humans,
pubmed-meshheading:15578088-Male,
pubmed-meshheading:15578088-Myocardial Contraction,
pubmed-meshheading:15578088-Myocardial Infarction,
pubmed-meshheading:15578088-Myocardium,
pubmed-meshheading:15578088-Myocytes, Cardiac,
pubmed-meshheading:15578088-Rats,
pubmed-meshheading:15578088-Rats, Sprague-Dawley,
pubmed-meshheading:15578088-S100 Proteins,
pubmed-meshheading:15578088-Sarcoplasmic Reticulum Calcium-Transporting ATPases
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pubmed:year |
2004
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pubmed:articleTitle |
Cardiac adenoviral S100A1 gene delivery rescues failing myocardium.
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pubmed:affiliation |
Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. patrick.most@jefferson.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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