Linked Life Data

16397146

Source:http://linkedlifedata.com/resource/pubmed/id/16397146

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-2-17
pubmed:abstractText
Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase used in the prevention of cardiovascular disease (CVD). In addition to their cholesterol-lowering activities, statins exert pleiotropic antiinflammatory effects, which might contribute to their beneficial effects not only on CVD but also on lipid-unrelated immune and inflammatory diseases, such as rheumatoid arthritis, asthma, stroke, and transplant rejection. However, the molecular mechanisms involved in these antiinflammatory properties of statins are unresolved. Here we show that the peroxisome proliferator-activated receptor (PPAR) alpha mediates antiinflammatory effects of simvastatin in vivo in models of acute inflammation. The inhibitory effects of statins on lipopolysaccharide-induced inflammatory response genes were abolished in PPARalpha-deficient macrophages and neutrophils. Moreover, simvastatin inhibited PPARalpha phosphorylation by lipopolysaccharide-activated protein kinase C (PKC) alpha. A constitutive active form of PKCalpha inhibited nuclear factor kappaB transrepression by PPARalpha whereas simvastatin enhanced transrepression activity of wild-type PPARalpha, but not of PPARalpha mutated in its PKC phosphorylation sites. These data indicate that the acute antiinflammatory effect of simvastatin occurs via PPARalpha by a mechanism involving inhibition of PKCalpha inactivation of PPARalpha transrepression activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
361-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Acute antiinflammatory properties of statins involve peroxisome proliferator-activated receptor-alpha via inhibition of the protein kinase C signaling pathway.
pubmed:affiliation
Institut Pasteur de Lille, Département d'Athérosclérose, INSERM, U545, Lille, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't