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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 |
2004-7-30
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pubmed:abstractText |
Many cardiovascular disease states end in progressive heart failure. Changes in intracellular calcium handling, including a reduced activity of the sarcoplasmic reticulum calcium pump (SERCA), contribute to this contractile dysfunction. As the regulatory protein phospholamban can inhibit the calcium pump, we evaluated it as a potential target to improve cardiac function. In this study, we describe a recombinant antibody-based protein (PLN-Ab) that binds to the cytoplasmic domain of phospholamban. Fluorescence resonance energy transfer (FRET) studies suggest that PLN-Ab mimics the effects of phospholamban phosphorylation. PLN-Ab accelerated the decay of the calcium transient when expressed in neonatal rat and adult mouse ventricular cardiac myocytes. In addition, direct injection of adenovirus encoding PLN-Ab into the diabetic mouse heart enhanced contractility when measured in vivo by echocardiography and in ex vivo Langendorff perfused hearts. The PLN-Ab provides a novel therapeutic approach to improving contractility through in vivo expression of an antibody inside cardiac myocytes.
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pubmed:grant |
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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 |
1530-6860
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pubmed:author |
pubmed-author:BelkeDarrell DDD,
pubmed-author:BluhmWolfgang FWF,
pubmed-author:CaryStephen PSP,
pubmed-author:DieterleThomasT,
pubmed-author:DillmannWolfgang HWH,
pubmed-author:HoPeterP,
pubmed-author:McDonoughPatrick MPM,
pubmed-author:MeyerMarkusM,
pubmed-author:ScottBrianB,
pubmed-author:SilvermanGregg JGJ,
pubmed-author:SwansonEricE,
pubmed-author:TrostSusanne USU
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pubmed:issnType |
Electronic
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1312-4
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15180962-Amino Acid Sequence,
pubmed-meshheading:15180962-Animals,
pubmed-meshheading:15180962-Antibody Specificity,
pubmed-meshheading:15180962-Base Sequence,
pubmed-meshheading:15180962-Calcium Signaling,
pubmed-meshheading:15180962-Calcium-Binding Proteins,
pubmed-meshheading:15180962-Calcium-Transporting ATPases,
pubmed-meshheading:15180962-Cardiotonic Agents,
pubmed-meshheading:15180962-Cell Line,
pubmed-meshheading:15180962-Chickens,
pubmed-meshheading:15180962-Diabetes Mellitus, Experimental,
pubmed-meshheading:15180962-Fluorescence Resonance Energy Transfer,
pubmed-meshheading:15180962-Gene Therapy,
pubmed-meshheading:15180962-Heart Failure,
pubmed-meshheading:15180962-Heart Ventricles,
pubmed-meshheading:15180962-Humans,
pubmed-meshheading:15180962-Immunoglobulins,
pubmed-meshheading:15180962-Kidney,
pubmed-meshheading:15180962-Mice,
pubmed-meshheading:15180962-Molecular Mimicry,
pubmed-meshheading:15180962-Molecular Sequence Data,
pubmed-meshheading:15180962-Myocardial Contraction,
pubmed-meshheading:15180962-Myocytes, Cardiac,
pubmed-meshheading:15180962-Peptide Fragments,
pubmed-meshheading:15180962-Phosphorylation,
pubmed-meshheading:15180962-Protein Binding,
pubmed-meshheading:15180962-Protein Structure, Tertiary,
pubmed-meshheading:15180962-Rats,
pubmed-meshheading:15180962-Recombinant Fusion Proteins
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pubmed:year |
2004
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pubmed:articleTitle |
A recombinant antibody increases cardiac contractility by mimicking phospholamban phosphorylation.
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pubmed:affiliation |
Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0618, 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
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