Title:
Controlled delivery of PDGF-BB, and endothelial-derived cardiomyocyte survival factor, for myocardial protection using injectable self-assembling peptide nanofibers

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dc.contributor.author Hsieh, Patrick C.H. en_US
dc.contributor.author Davis, Michael E. en_US
dc.contributor.author Gannon, Joseph en_US
dc.contributor.author MacGillivray, Catherine en_US
dc.contributor.author Lee, Richard T. en_US
dc.contributor.corporatename Harvard Medical School en_US
dc.contributor.corporatename Brigham and Women’s Hospital. Cardiovascular Division en_US
dc.contributor.corporatename Brigham and Women's Hospital. Dept. of Medicine en_US
dc.date.accessioned 2013-06-03T20:16:36Z
dc.date.available 2013-06-03T20:16:36Z
dc.date.issued 2006-01
dc.description © 2006 The American Society for Clinical Investigation en_US
dc.description The electronic version of this article is the complete one and can be found online at: http://www.jci.org/articles/view/25878 en_US
dc.description DOI: 10.1172/JCI25878 en_US
dc.description.abstract Endothelial cells can protect cardiomyocytes from injury, but the mechanism of this protection is incompletely described. Here we demonstrate that protection of cardiomyocytes by endothelial cells occurs through PDGF-BB signaling. PDGF-BB induced cardiomyocyte Akt phosphorylation in a time- and dose-dependent manner and prevented apoptosis via PI3K/Akt signaling. Using injectable self-assembling peptide nanofibers, which bound PDGF-BB in vitro, sustained delivery of PDGF-BB to the myocardium at the injected sites for 14 days was achieved. A blinded and randomized study in 96 rats showed that injecting nanofibers with PDGF-BB, but not nanofibers or PDGF-BB alone, decreased cardiomyocyte death and preserved systolic function after myocardial infarction. A separate blinded and randomized study in 52 rats showed that PDGF-BB delivered with nanofibers decreased infarct size after ischemia/reperfusion. PDGF-BB with nanofibers induced PDGFR-β and Akt phosphorylation in cardiomyocytes in vivo. These data demonstrate that endothelial cells protect cardiomyocytes via PDGF-BB signaling and that this in vitro finding can be translated into an effective in vivo method of protecting myocardium after infarction. Furthermore, this study shows that injectable nanofibers allow precise and sustained delivery of proteins to the myocardium with potential therapeutic benefits. en_US
dc.identifier.citation Patrick C.H. Hsieh, Michael E. Davis, Joseph Gannon, Catherine MacGillivray and Richard T. Lee, “Controlled delivery of PDGF-BB, and endothelial-derived cardiomyocyte survival factor, for myocardial protection using injectable self-assembling peptide nanofibers,” Journal of Clinical Investigation, 116, 1, 237-248(January 2006) en_US
dc.identifier.doi 10.1172/JCI25878
dc.identifier.issn 0021-9738
dc.identifier.uri http://hdl.handle.net/1853/47162
dc.language.iso en_US en_US
dc.publisher Georgia Institute of Technology en_US
dc.publisher.original American Society for Clinical Investigation en_US
dc.subject Endothelial cells en_US
dc.subject Cardiomyocytes en_US
dc.subject Cardiomyocyte survival factor en_US
dc.subject PDGF-BB signaling en_US
dc.title Controlled delivery of PDGF-BB, and endothelial-derived cardiomyocyte survival factor, for myocardial protection using injectable self-assembling peptide nanofibers en_US
dc.type Text
dc.type.genre Article
dspace.entity.type Publication
local.contributor.author Davis, Michael E.
local.contributor.corporatename Wallace H. Coulter Department of Biomedical Engineering
local.contributor.corporatename College of Engineering
relation.isAuthorOfPublication fab83195-e1b0-4b5e-933d-5b97a14b945a
relation.isOrgUnitOfPublication da59be3c-3d0a-41da-91b9-ebe2ecc83b66
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
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