| Targeting epoxides for organ damage in hypertension. | |
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MedLine Citation:
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PMID: 20531214 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid and EETs have a number of beneficial cardiovascular actions. This has led to the concept that EETs and its metabolic pathway can be therapeutically targeted for hypertension and other cardiovascular diseases. One approach has been to prevent the conversion of EETs to their inactive diols by inhibiting the soluble epoxide hydrolase (sEH) enzyme. Inhibition of sEH has been demonstrated to decrease blood pressure in certain experimental models of hypertension, decrease inflammation, and protect organs from damage associated with hypertension and other cardiovascular diseases. The development of sEH inhibitors has reached the point where they are being evaluated in humans. A second therapeutic approach has been to develop EET agonists. EET agonists have been essential for determining the structure function relationship for EETs and determining cell-signaling mechanisms by which EETs exert their cardiovascular actions. More recently, EET agonists have been administered chronically to experimental animal models of hypertension and metabolic syndrome and have been demonstrated to decrease blood pressure, improve insulin signaling, and improve vascular function. These experimental findings provide evidence for sEH inhibitors and EET agonists as a therapeutic approach for cardiovascular diseases, hypertension, and the associated end-organ damage. |
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Authors:
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John D Imig |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 56 ISSN: 1533-4023 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-13 Completed Date: 2011-03-10 Revised Date: 2012-05-07 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 329-35 Citation Subset: IM |
Affiliation:
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Department of Pharmacology & Toxicology, Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. jdimig@mcw.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Eicosanoids / agonists, metabolism* Epoxide Hydrolases / antagonists & inhibitors*, metabolism Epoxy Compounds / metabolism* Humans Hypertension / drug therapy*, enzymology, physiopathology Molecular Targeted Therapy |
| Grant Support | |
ID/Acronym/Agency:
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DK38226/DK/NIDDK NIH HHS; HL59699/HL/NHLBI NIH HHS; P01 DK038226-25/DK/NIDDK NIH HHS; R01 HL059699-13/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Eicosanoids; 0/Epoxy Compounds; EC 3.3.2.-/Epoxide Hydrolases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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