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

45 Citations (Scopus)

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

Fingerprint

Epoxide Hydrolases
Neointima
Thigh
Femoral Artery
Carotid Arteries
Apolipoproteins E
Bromodeoxyuridine
Smooth Muscle Myocytes
Ligation
Anti-Inflammatory Agents
Macrophages
Cell Proliferation

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Soluble epoxide hydrolase deficiency attenuates neointima formation in the femoral cuff model of hyperlipidemic mice. / Revermann, Marc; Schloss, Manuel; Barbosa-Sicard, Eduardo; Mieth, Anja; Liebner, Stefan; Morisseau, Christophe; Geisslinger, Gerd; Schermuly, Ralph T.; Fleming, Ingrid; Hammock, Bruce D.; Brandes, Ralf P.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 30, No. 5, 05.2010, p. 909-914.

Research output: Contribution to journalArticle

Revermann, M, Schloss, M, Barbosa-Sicard, E, Mieth, A, Liebner, S, Morisseau, C, Geisslinger, G, Schermuly, RT, Fleming, I, Hammock, BD & Brandes, RP 2010, 'Soluble epoxide hydrolase deficiency attenuates neointima formation in the femoral cuff model of hyperlipidemic mice', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 5, pp. 909-914. https://doi.org/10.1161/ATVBAHA.110.204099
Revermann, Marc ; Schloss, Manuel ; Barbosa-Sicard, Eduardo ; Mieth, Anja ; Liebner, Stefan ; Morisseau, Christophe ; Geisslinger, Gerd ; Schermuly, Ralph T. ; Fleming, Ingrid ; Hammock, Bruce D. ; Brandes, Ralf P. / Soluble epoxide hydrolase deficiency attenuates neointima formation in the femoral cuff model of hyperlipidemic mice. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2010 ; Vol. 30, No. 5. pp. 909-914.
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