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Cytochrome P450-dependent eicosanoid production and crosstalk.
MedLine Citation:
PMID:  21825980     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: This review highlights recent advances in eicosanoid biology, especially linked to the cytochrome P450 (CYP)/soluble epoxide hydrolase (sEH) axis in vascular biology and disease. RECENT FINDINGS: Since the first reports that CYP-derived metabolites of arachidonic acid can elicit vascular smooth muscle hyperpolarization and relaxation, it has become clear that fatty acid epoxides and diols are important lipid signaling molecules. Targeting CYP epoxygenases in vivo is difficult as these enzymes are involved in the metabolism of many currently used clinical agents. However, targeting the sEH which metabolizes fatty acid epoxides to their corresponding diols is a highly effective way of manipulating levels of these lipid mediators in vivo. Indeed, sEH mice are protected against the development of some forms of hypertension, and have altered adipocyte metabolism and insulin resistance, phenomena reproduced by selective sEH inhibitors. SUMMARY: Given that elevated epoxide levels have been linked with decreased blood pressure and inflammation in animal models, inhibitors of the sEH are currently being developed for the treatment of human hypertension and inflammation/atherosclerosis. This review focuses on outlining recent insights gained in the beneficial as well as the potentially adverse aspects of interfering with the CYP/sEH axis.
Authors:
Ingrid Fleming
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-5
Journal Detail:
Title:  Current opinion in lipidology     Volume:  -     ISSN:  1473-6535     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010000     Medline TA:  Curr Opin Lipidol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt, Germany.
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