Soluble epoxide hydrolase inhibition modulates vascular remodeling. Am J Physiol Heart Circ Physiol 2010 Mar;298(3):H795-806
Date
12/26/2009Pubmed ID
20035028Pubmed Central ID
PMC2838550DOI
10.1152/ajpheart.00543.2009Scopus ID
2-s2.0-77749279557 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
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.
Author List
Simpkins AN, Rudic RD, Roy S, Tsai HJ, Hammock BD, Imig JDMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Carotid Arteries
Carotid Artery Injuries
Cell Proliferation
Endothelium, Vascular
Epoxide Hydrolases
Hyperplasia
Lauric Acids
Ligation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Animal
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Tunica Intima