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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2010-6-14
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pubmed:abstractText |
Cardiac fibrosis is a consequence of many cardiovascular diseases and contributes to impaired ventricular function. Activation of the prostacyclin receptor (IP) protects against cardiac fibrosis, but the molecular mechanisms are not totally understood. Using mouse cardiac fibroblasts, we found that IP activation with cicaprost suppressed expression of collagen I and other target genes of transforming growth factor-beta. This effect of cicaprost was unlikely to be mediated by inhibition of the Smad2/3 or mitogen-activated protein kinase (MAPK) activities, but was associated with cAMP elevation and phosphorylation of the transcription factor cAMP response element binding protein (CREB). Expression of a non-phosphorylated CREB mutant suppressed the inhibitory effect of cicaprost. It appears that phosphorylated CREB binds to and sequestrates the transcription coactivator CBP/p300 from binding to Smad. Inhibition of the intrinsic histone acetyl-transferase activity of CBP/p300 with garcinol significantly suppressed collagen I expression in fibroblasts. Using apolipoprotein E and IP double knockout mouse, we demonstrated that endogenous prostacyclin/IP signaling had an inhibitory effect on angiotensin II-induced cardiac fibrosis under hypercholesterolemic conditions. Taken together, our results suggest that the prostacyclin/IP pathway suppresses cardiac fibrosis, at least partly, by inducing CREB phosphorylation.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/E1A-Associated p300 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Ep300 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Epoprostenol,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Epoprostenol,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/cicaprost
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1095-8584
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
176-85
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pubmed:meshHeading |
pubmed-meshheading:20403362-Angiotensin II,
pubmed-meshheading:20403362-Animals,
pubmed-meshheading:20403362-Cell Separation,
pubmed-meshheading:20403362-Collagen,
pubmed-meshheading:20403362-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:20403362-Down-Regulation,
pubmed-meshheading:20403362-E1A-Associated p300 Protein,
pubmed-meshheading:20403362-Epoprostenol,
pubmed-meshheading:20403362-Fibroblasts,
pubmed-meshheading:20403362-Fibrosis,
pubmed-meshheading:20403362-Hyperlipidemias,
pubmed-meshheading:20403362-Mice,
pubmed-meshheading:20403362-Mice, Knockout,
pubmed-meshheading:20403362-Models, Biological,
pubmed-meshheading:20403362-Myocardium,
pubmed-meshheading:20403362-NADPH Oxidase,
pubmed-meshheading:20403362-Phosphorylation,
pubmed-meshheading:20403362-Receptors, Epoprostenol,
pubmed-meshheading:20403362-Signal Transduction,
pubmed-meshheading:20403362-Transforming Growth Factor beta
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pubmed:year |
2010
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pubmed:articleTitle |
Prostacyclin receptor suppresses cardiac fibrosis: role of CREB phosphorylation.
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pubmed:affiliation |
O'Brien Institute, University of Melbourne, Fitzroy, Victoria 3065, Australia. chane@unimelb.edu.au
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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