Source:http://linkedlifedata.com/resource/pubmed/id/16714359
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2006-9-15
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| pubmed:abstractText |
Angiotensin II (ANG II), a product of renin-angiotensin system activation, enhances collagen synthesis, which is a key event in cardiac remodeling after myocardial infarction. Inhibition of cardiac remodeling is now a target of multiple therapies, including 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as statins, and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands. We examined the potential antifibrotic effect of the combination of a statin (pravastatin) and a PPAR-gamma ligand (pioglitazone) in ANG II-treated mouse cardiac fibroblasts. ANG II treatment induced procollagen-1 expression, which was inhibited by pravastatin and pioglitazone in a dose-dependent fashion. Pretreatment of fibroblasts with low therapeutic concentrations of either pravastatin (0.1 microM) or pioglitazone (5 microM) only slightly decreased ANG II-induced NADPH oxidase expression, superoxide anion production, and procollagen-1 expression; however, the combination of pravastatin and pioglitazone markedly modulated these effects of ANG II. The combination also blocked ANG II-mediated p38 MAPK and p44/42 MAPK activation. Electrophoretic mobility shift assay showed that ANG II activated transcription factors NF-kappaB and activator protein-1 (AP-1). Although pravastatin and pioglitazone alone had a variable effect on NF-kappaB and AP-1 activation, their combination exerted a potent inhibitory effect on the activation of both NF-kappaB and AP-1. The effects of pravastatin and pioglitazone in combination on superoxide generation and procollagen-1 expression mimicked those of alpha-tocopherol and gamma-tocopherol, two potent antioxidants. Thus it appears that there is a positive interaction between pravastatin and pioglitazone in modulating ANG II-mediated oxidative stress, inhibiting MAPK activation, and procollagen-1 expression.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl-CoA...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Pravastatin,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones,
http://linkedlifedata.com/resource/pubmed/chemical/Tocopherols,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/pioglitazone
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0363-6135
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
291
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
H1738-45
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16714359-Angiotensin II,
pubmed-meshheading:16714359-Animals,
pubmed-meshheading:16714359-Antioxidants,
pubmed-meshheading:16714359-Cells, Cultured,
pubmed-meshheading:16714359-Collagen Type I,
pubmed-meshheading:16714359-Drug Synergism,
pubmed-meshheading:16714359-Fibroblasts,
pubmed-meshheading:16714359-Gene Expression Regulation,
pubmed-meshheading:16714359-Hydroxymethylglutaryl-CoA Reductase Inhibitors,
pubmed-meshheading:16714359-Mice,
pubmed-meshheading:16714359-Mice, Inbred C57BL,
pubmed-meshheading:16714359-Mitogen-Activated Protein Kinases,
pubmed-meshheading:16714359-Myocardium,
pubmed-meshheading:16714359-NF-kappa B,
pubmed-meshheading:16714359-Oxidative Stress,
pubmed-meshheading:16714359-Pravastatin,
pubmed-meshheading:16714359-RNA, Messenger,
pubmed-meshheading:16714359-Superoxides,
pubmed-meshheading:16714359-Thiazolidinediones,
pubmed-meshheading:16714359-Tocopherols,
pubmed-meshheading:16714359-Transcription Factor AP-1
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| pubmed:year |
2006
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| pubmed:articleTitle |
Angiotensin II-mediated oxidative stress and procollagen-1 expression in cardiac fibroblasts: blockade by pravastatin and pioglitazone.
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| pubmed:affiliation |
Division of Cardiovascular Medicine, Univ. of Arkansas for Medical Sciences, 4301 West Markham St., Slot 532, Little Rock, AR 72205-7199, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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