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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2002-8-1
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pubmed:abstractText |
The feasibility of gene therapy for cardiomyopathy, heart failure and other chronic cardiac muscle diseases is so far unproven. Here, we developed an in vivo recombinant adeno-associated virus (rAAV) transcoronary delivery system that allows stable, high efficiency and relatively cardiac-selective gene expression. We used rAAV to express a pseudophosphorylated mutant of human phospholamban (PLN), a key regulator of cardiac sarcoplasmic reticulum (SR) Ca(2+) cycling in BIO14.6 cardiomyopathic hamsters. The rAAV/S16EPLN treatment enhanced myocardial SR Ca(2+) uptake and suppressed progressive impairment of left ventricular (LV) systolic function and contractility for 28-30 weeks, thereby protecting cardiac myocytes from cytopathic plasma-membrane disruption. Low LV systolic pressure and deterioration in LV relaxation were also largely prevented by rAAV/S16EPLN treatment. Thus, transcoronary gene transfer of S16EPLN via rAAV vector is a potential therapy for progressive dilated cardiomyopathy and associated heart failure.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1078-8956
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pubmed:author |
pubmed-author:ChienKenneth RKR,
pubmed-author:DateMoto-oMO,
pubmed-author:GuYusuY,
pubmed-author:HoshijimaMasahikoM,
pubmed-author:IkedaYasuhiroY,
pubmed-author:IwanagaYoshitakaY,
pubmed-author:IwatateMitsuoM,
pubmed-author:LiManxiangM,
pubmed-author:MinamisawaSusumuS,
pubmed-author:RossJohnJJr,
pubmed-author:WangLiliL,
pubmed-author:WangYibinY,
pubmed-author:WilsonJames MJM
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pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
864-71
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12134142-Adenosine Triphosphatases,
pubmed-meshheading:12134142-Amino Acid Sequence,
pubmed-meshheading:12134142-Animals,
pubmed-meshheading:12134142-Aorta,
pubmed-meshheading:12134142-Calcium,
pubmed-meshheading:12134142-Calcium-Binding Proteins,
pubmed-meshheading:12134142-Cardiac Output, Low,
pubmed-meshheading:12134142-Cells, Cultured,
pubmed-meshheading:12134142-Cricetinae,
pubmed-meshheading:12134142-Dependovirus,
pubmed-meshheading:12134142-Disease Progression,
pubmed-meshheading:12134142-Gene Therapy,
pubmed-meshheading:12134142-Gene Transfer Techniques,
pubmed-meshheading:12134142-Genetic Vectors,
pubmed-meshheading:12134142-Hemodynamics,
pubmed-meshheading:12134142-Humans,
pubmed-meshheading:12134142-Liver,
pubmed-meshheading:12134142-Mice,
pubmed-meshheading:12134142-Molecular Sequence Data,
pubmed-meshheading:12134142-Mutation,
pubmed-meshheading:12134142-Myocardium,
pubmed-meshheading:12134142-Sarcoplasmic Reticulum,
pubmed-meshheading:12134142-Sequence Alignment
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pubmed:year |
2002
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pubmed:articleTitle |
Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery.
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pubmed:affiliation |
University of California, San Diego Institute of Molecular Medicine, La Jolla, California, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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