Soluble epoxide hydrolase in atherosclerosis

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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

Fingerprint

Epoxide Hydrolases
Eicosanoids
Atherosclerosis
Acids
Cardiovascular Diseases
Apolipoproteins E
Therapeutic Uses
LDL Lipoproteins
Antihypertensive Agents
Aneurysm
Blood Pressure
Inflammation
Genes
Proteins

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)

Cite this

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

Soluble epoxide hydrolase in atherosclerosis. / Wang, Yi Xin Jim; Ulu, Arzu; Zhang, Le Ning; Hammock, Bruce.

In: Current Atherosclerosis Reports, Vol. 12, No. 3, 05.2010, p. 174-183.

Research output: Contribution to journalArticle

Wang, YXJ, Ulu, A, Zhang, LN & Hammock, B 2010, 'Soluble epoxide hydrolase in atherosclerosis', Current Atherosclerosis Reports, vol. 12, no. 3, pp. 174-183. https://doi.org/10.1007/s11883-010-0108-5
Wang, Yi Xin Jim ; Ulu, Arzu ; Zhang, Le Ning ; Hammock, Bruce. / Soluble epoxide hydrolase in atherosclerosis. In: Current Atherosclerosis Reports. 2010 ; Vol. 12, No. 3. pp. 174-183.
@article{9d1d9b36f0a4435096f1d54270dcea47,
title = "Soluble epoxide hydrolase in atherosclerosis",
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.",
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",
author = "Wang, {Yi Xin Jim} and Arzu Ulu and Zhang, {Le Ning} and Bruce Hammock",
year = "2010",
month = "5",
doi = "10.1007/s11883-010-0108-5",
language = "English (US)",
volume = "12",
pages = "174--183",
journal = "Current Atherosclerosis Reports",
issn = "1523-3804",
publisher = "Current Medicine Group",
number = "3",

}

TY - JOUR

T1 - Soluble epoxide hydrolase in atherosclerosis

AU - Wang, Yi Xin Jim

AU - Ulu, Arzu

AU - Zhang, Le Ning

AU - Hammock, Bruce

PY - 2010/5

Y1 - 2010/5

N2 - 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.

AB - 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.

KW - Abdominal aortic aneurysm

KW - Angiotensin II

KW - Apolipoprotein E deficient mice

KW - Atherosclerosis

KW - Cytochrome P450

KW - DHET

KW - Dihydroxyeicosatrienoic acid

KW - EET

KW - Eicosanoids

KW - Ephx2 gene polymorphisms

KW - Epoxyeicosatrienoic acid

KW - SEH

KW - Soluble epoxide hydrolase

UR - http://www.scopus.com/inward/record.url?scp=77953538299&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953538299&partnerID=8YFLogxK

U2 - 10.1007/s11883-010-0108-5

DO - 10.1007/s11883-010-0108-5

M3 - Article

VL - 12

SP - 174

EP - 183

JO - Current Atherosclerosis Reports

JF - Current Atherosclerosis Reports

SN - 1523-3804

IS - 3

ER -