| Soluble epoxide hydrolase deficiency attenuates neointima formation in the femoral cuff model of hyperlipidemic mice. | |
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MedLine Citation:
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PMID: 20224052 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Epoxyeicosatrienoic acids (EETs) have antiinflammatory effects and are required for normal endothelial function. The soluble epoxide hydrolase (sEH) metabolizes EETs to their less active diols. We hypothesized that knockout and inhibition of sEH prevents neointima formation in hyperlipidemic ApoE(-/-) mice. METHODS AND RESULTS: Inhibition of sEH by 12-(3-adamantan-1-yl-ureido) dodecanoic acid or knockout of the enzyme significantly increased plasma EET levels. sEH activity was detectable in femoral and carotid arteries. sEH knockout or inhibition resulted in a significant reduction of neointima formation in the femoral artery cuff model but not following carotid artery ligation. Although macrophage infiltration occurred abundantly at the site of cuff placement in both sEH(+/+) and sEH(-/-), the expression of proinflammatory genes was significantly reduced in femoral arteries from sEH(-/-) mice. Moreover, an in vivo 5-bromo-2'-deoxyuridine assay revealed that smooth muscle cell proliferation at the site of cuff placement was attenuated in sEH knockout and sEH inhibitor-treated animals. CONCLUSION: These observations suggest that inhibition of sEH prevents vascular remodeling in an inflammatory model but not in a blood flow-dependent model of neointima formation. |
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Authors:
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Marc Revermann; Manuel Schloss; Eduardo Barbosa-Sicard; Anja Mieth; Stefan Liebner; Christophe Morisseau; Gerd Geisslinger; Ralph T Schermuly; Ingrid Fleming; Bruce D Hammock; Ralf P Brandes |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-03-11 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-15 Completed Date: 2010-05-03 Revised Date: 2013-05-30 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 909-14 Citation Subset: IM |
Affiliation:
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Institut für Kardiovaskuläre Physiologie, Fachbereich Medizin der Goethe-Universität, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adamantane
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analogs & derivatives*,
pharmacology Animals Apolipoproteins E / deficiency, genetics Arachidonic Acids / metabolism Atherosclerosis / enzymology, etiology, genetics, pathology, prevention & control* Carotid Artery Diseases / enzymology, pathology, prevention & control Carotid Artery, Common / drug effects, enzymology, pathology Cell Proliferation / drug effects Disease Models, Animal Enzyme Inhibitors / pharmacology* Epoxide Hydrolases / antagonists & inhibitors*, deficiency*, genetics, metabolism Femoral Artery / drug effects*, enzymology, injuries, pathology Hyperlipidemias / complications*, enzymology, genetics Hyperplasia Inflammation Mediators / metabolism Lauric Acids / pharmacology* Macrophages / pathology Mice Mice, Inbred C57BL Mice, Knockout Muscle, Smooth, Vascular / drug effects*, enzymology, injuries, pathology Tunica Intima / drug effects*, enzymology, injuries, pathology |
| Grant Support | |
ID/Acronym/Agency:
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HL59699/HL/NHLBI NIH HHS; R37 ER02710//PHS HHS; R37 ES002710-27/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/12-(3-adamantan-1-ylureido)dodecanoic acid; 0/Apolipoproteins E; 0/Arachidonic Acids; 0/Enzyme Inhibitors; 0/Inflammation Mediators; 0/Lauric Acids; 281-23-2/Adamantane; 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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