Soluble epoxide hydrolase deficiency attenuates neointima formation in the femoral cuff model of hyperlipidemic mice

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

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)909-914
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume30
Issue number5
DOIs
StatePublished - May 2010

Keywords

  • Epoxyeicosatrienoic acids
  • Lipid mediators
  • Migration
  • Neointima
  • Smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Revermann, M., Schloss, M., Barbosa-Sicard, E., Mieth, A., Liebner, S., Morisseau, C., Geisslinger, G., Schermuly, R. T., Fleming, I., Hammock, B. D., & Brandes, R. P. (2010). Soluble epoxide hydrolase deficiency attenuates neointima formation in the femoral cuff model of hyperlipidemic mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(5), 909-914. https://doi.org/10.1161/ATVBAHA.110.204099