Soluble epoxide hydrolase in atherosclerosis

Yi Xin Jim Wang, Arzu Ulu, Le Ning Zhang, Bruce Hammock

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Like many eicosanoids, epoxyeicosatrienoic acids (EETs) have multiple biological functions, including reduction of blood pressure, inflammation, and atherosclerosis in multiple species. Hydration of EETs by the soluble epoxide hydrolase (sEH) is the major route of their degradation to the less bioactive diols. Inhibition of the sEH stabilizes EETs, thus, enhancing the beneficial effects of EETs. Human data show an association of sEH (Ephx2) gene polymorphisms with increased risk of atherosclerosis and cardiovascular diseases. These data suggest a potential therapeutic effect of sEH inhibitors (sEHI) in the treatment of atherosclerosis. Indeed, two laboratories reported independently that using different sEHIs in apolipoprotein E-deficient mice significantly attenuated atherosclerosis development and aneurysm formation. The antiatherosclerotic effects of sEHI are correlatedwith elevation in EET levels and associated with reduction of low-density lipoprotein and elevation of highdensity lipoprotein cholesterols, as well as attenuation of expression of proinflammatory genes and proteins. In addition, the antihypertensive effects and improvement of endothelial function also contribute to the mechanism of the antiatherosclerotic effects of sEHI. The broad spectrum of biological action of EETs and sEHIs with multiple biological beneficial actions provides a promising new class of therapeutics for atherosclerosis and other cardiovascular diseases.

Original languageEnglish (US)
Pages (from-to)174-183
Number of pages10
JournalCurrent Atherosclerosis Reports
Volume12
Issue number3
DOIs
StatePublished - May 2010

Keywords

  • Abdominal aortic aneurysm
  • Angiotensin II
  • Apolipoprotein E deficient mice
  • Atherosclerosis
  • Cytochrome P450
  • DHET
  • Dihydroxyeicosatrienoic acid
  • EET
  • Eicosanoids
  • Ephx2 gene polymorphisms
  • Epoxyeicosatrienoic acid
  • SEH
  • Soluble epoxide hydrolase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

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    Wang, Y. X. J., Ulu, A., Zhang, L. N., & Hammock, B. (2010). Soluble epoxide hydrolase in atherosclerosis. Current Atherosclerosis Reports, 12(3), 174-183. https://doi.org/10.1007/s11883-010-0108-5