Linked Life Data

17655859

Source:http://linkedlifedata.com/resource/pubmed/id/17655859

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-10-1
pubmed:abstractText
Epsilon protein kinase C (epsilonPKC) plays pivotal roles in myocardial infarction and in heart failure. Although cardiac transplantation is a well-established therapy for severe heart failure, allograft rejection and host inflammatory responses limit graft function and reduce life expectancy. Here we determined whether sustained epsilonPKC inhibition beginning 3 days after transplantation suppress allograft rejection and improve cardiac transplantation using a murine heterotopic transplantation model. Hearts of FVB mice (H-2(q)) were transplanted into C57BL/6 mice (H-2(b)). Delivery of the epsilonPKC inhibitor, TAT(47-57)-epsilonV1-2 (epsilonV1-2, n=9, 20 mg/kg/day), or the carrier control peptide, TAT(47-57) (TAT, n=8), by osmotic pump began 3 days after transplantation and continued for the remaining 4 weeks. epsilonV1-2 treatment significantly improved the beating score throughout the treatment. Infiltration of macrophages and T cells into the cardiac grafts was significantly reduced and parenchymal fibrosis was decreased in animals treated with epsilonV1-2 as compared with control treatment. Finally, the rise in pro-fibrotic cytokine, TGF-beta and monocyte recruiting chemokine MCP-1 levels was almost abolished by epsilonV1-2 treatment, whereas the rise in PDGF-BB level was unaffected. These data suggest that epsilonPKC activity contributes to the chronic immune response in cardiac allograft and that an epsilonPKC-selective inhibitor, such as epsilonV1-2, could augment current therapeutic strategies to suppress inflammation and prolong graft survival in humans.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
517-22
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17655859-Animals, pubmed-meshheading:17655859-Chronic Disease, pubmed-meshheading:17655859-Cyclosporine, pubmed-meshheading:17655859-Disease Models, Animal, pubmed-meshheading:17655859-Graft Rejection, pubmed-meshheading:17655859-Graft Survival, pubmed-meshheading:17655859-Heart Failure, pubmed-meshheading:17655859-Heart Transplantation, pubmed-meshheading:17655859-Immunosuppression, pubmed-meshheading:17655859-Immunosuppressive Agents, pubmed-meshheading:17655859-Macrophages, pubmed-meshheading:17655859-Male, pubmed-meshheading:17655859-Mice, pubmed-meshheading:17655859-Mice, Inbred C57BL, pubmed-meshheading:17655859-Myocarditis, pubmed-meshheading:17655859-Neutrophil Infiltration, pubmed-meshheading:17655859-Peptide Fragments, pubmed-meshheading:17655859-Protein Kinase C, pubmed-meshheading:17655859-Protein Kinase C-epsilon, pubmed-meshheading:17655859-Protein Kinase Inhibitors, pubmed-meshheading:17655859-T-Lymphocytes, pubmed-meshheading:17655859-Transplantation, Heterotopic
pubmed:year
2007
pubmed:articleTitle
Pharmacological inhibition of epsilon PKC suppresses chronic inflammation in murine cardiac transplantation model.
pubmed:affiliation
Department of Chemical and Systems Biology, Stanford University School of Medicine CCSR, Rm 3145A, 269 Campus Drive Stanford, CA 94305-5174, USA.
pubmed:publicationType
Journal Article, Evaluation Studies, Research Support, N.I.H., Extramural