Soluble epoxide hydrolase inhibition modulates vascular remodeling

A. N. Simpkins, Radu Daniel Rudic, S. Roy, H. J. Tsai, B. D. Hammock, J. D. Imig

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The soluble epoxide hydrolase enzyme (SEH) and vascular remodeling are associated with cardiovascular disease. Although inhibition of SEH prevents smooth muscle cell proliferation in vitro, the effects of SEH inhibition on vascular remodeling in vivo and mechanisms of these effects remain unclear. Herein we determined the effects of SEH antagonism in an endothelium intact model of vascular remodeling induced by flow reduction and an endothelium denuded model of vascular injury. We demonstrated that chronic treatment of spontaneously hypertensive stroke-prone rats with 12-(3-adamantan-1-yl-ureido) dodecanoic acid, an inhibitor of SEH, improved the increment of inward remodeling induced by common carotid ligation to a level that was comparable with normotensive Wistar Kyoto rats. Similarly, mice with deletion of the gene responsible for the production of the SEH enzyme (Ephx2 -/- ) demonstrated enhanced inward vascular remodeling induced by carotid ligation. However, the hyperplastic response induced by vascular injury that denudes the endothelium was unabated by SEH inhibition or Ephx2 gene deletion. These results suggest that SEH inhibition or Ephx2 gene deletion antagonizes neointimal formation in vivo by mechanisms that are endothelium dependent. Thus SEH inhibition may have therapeutic potential for flow-induced remodeling and neointimal formation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume298
Issue number3
DOIs
StatePublished - Mar 1 2010

Fingerprint

Epoxide Hydrolases
Enzymes
Endothelium
Gene Deletion
Vascular System Injuries
Ligation
Vascular Remodeling
Inbred WKY Rats
Smooth Muscle Myocytes
Cardiovascular Diseases
Stroke
Cell Proliferation

Keywords

  • Endothelium
  • Epoxyeicosatrienoic acids
  • Hyperplasia
  • Hypertension
  • Hypertrophy
  • Mice

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Soluble epoxide hydrolase inhibition modulates vascular remodeling. / Simpkins, A. N.; Rudic, Radu Daniel; Roy, S.; Tsai, H. J.; Hammock, B. D.; Imig, J. D.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 298, No. 3, 01.03.2010.

Research output: Contribution to journalArticle

Simpkins, A. N. ; Rudic, Radu Daniel ; Roy, S. ; Tsai, H. J. ; Hammock, B. D. ; Imig, J. D. / Soluble epoxide hydrolase inhibition modulates vascular remodeling. In: American Journal of Physiology - Heart and Circulatory Physiology. 2010 ; Vol. 298, No. 3.
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