A recombinant antibody increases cardiac contractility by mimicking phospholamban phosphorylation
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4507749
Author(s) Meyer, Markus; Belke, Darrell D.; Trost, Susanne U.; Swanson, Eric; Dieterle, Thomas; Scott, Brian; Cary, Stephen P.; Ho, Peter; Bluhm, Wolfgang F.; McDonough, Patrick M.; Silverman, Gregg J.; Dillmann, Wolfgang H.
Author(s) at UniBasel Dieterle, Thomas
Year 2004
Title A recombinant antibody increases cardiac contractility by mimicking phospholamban phosphorylation
Journal FASEB Journal
Volume 18
Number 9
Pages / Article-Number 1312-+
Mesh terms Amino Acid Sequence; Animals; Antibody Specificity; Base Sequence; Calcium Signaling, drug effects; Calcium-Binding Proteins, chemistry; Calcium-Transporting ATPases, metabolism; Cardiotonic Agents, chemistry, pharmacology; Cell Line, drug effects; Chickens; Diabetes Mellitus, Experimental, metabolism; Fluorescence Resonance Energy Transfer; Genetic Therapy; Heart Failure, diagnostic imaging, therapy; Heart Ventricles, cytology; Humans; Immunoglobulins, genetics, immunology, pharmacology; Kidney; Mice; Molecular Mimicry; Molecular Sequence Data; Myocardial Contraction, drug effects; Myocytes, Cardiac, drug effects, physiology; Peptide Fragments, chemistry, immunology; Phosphorylation; Protein Binding; Protein Structure, Tertiary; Rats; Recombinant Fusion Proteins, genetics, pharmacology; Ultrasonography
Abstract 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.
Publisher Federation of American Society of Experimental Biology
ISSN/ISBN 0892-6638 ; 1530-6860
URL https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.03-1231fje
edoc-URL https://edoc.unibas.ch/71058/
Full Text on edoc No
Digital Object Identifier DOI 10.1096/fj.03-1231fje
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/15180962
ISI-Number WOS:000222327500027
Document type (ISI) Article
 
   

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