PMID- 23585883
OWN - NLM
STAT- MEDLINE
DCOM- 20131022
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 4
DP  - 2013
TI  - Role of endothelial soluble epoxide hydrolase in cerebrovascular function and 
      ischemic injury.
PG  - e61244
LID - 10.1371/journal.pone.0061244 [doi]
LID - e61244
AB  - Soluble Epoxide Hydrolase (sEH) is a key enzyme in the metabolism and termination 
      of action of epoxyeicosatrienoic acids, derivatives of arachidonic acid, which 
      are protective against ischemic stroke. Mice lacking sEH globally are protected 
      from injury following stroke; however, little is known about the role of 
      endothelial sEH in brain ischemia. We generated transgenic mice with 
      endothelial-specific expression of human sEH (Tie2-hsEH), and assessed the effect 
      of transgenic overexpression of endothelial sEH on endothelium-dependent vascular 
      reactivity and ischemic injury following middle cerebral artery occlusion (MCAO). 
      Compared to wild-type, male Tie2-hsEH mice exhibited impaired vasodilation in 
      response to stimulation with 1 microM acetylcholine as assessed by laser-Doppler 
      perfusion monitoring in an in-vivo cranial window preparation. No difference in 
      infarct size was observed between wild-type and Tie2-hsEH male mice. In females, 
      however, Tie2-hsEH mice sustained larger infarcts in striatum, but not cortex, 
      compared to wild-type mice. Sex difference in ischemic injury was maintained in 
      the cortex of Tie2-hsEH mice. In the striatum, expression of Tie2-hsEH resulted 
      in a sex difference, with larger infarct in females than males. These findings 
      demonstrate that transgenic expression of sEH in endothelium results in impaired 
      endothelium-dependent vasodilation in the cerebral circulation, and that females 
      are more susceptible to enhanced ischemic damage as a result of increased 
      endothelial sEH than males, especially in end-arteriolar striatal region.
FAU - Zhang, Wenri
AU  - Zhang W
AD  - Department of Anesthesiology and Perioperative Medicine, Oregon Health and 
      Science University, Portland, Oregon, United States of America.
FAU - Davis, Catherine M
AU  - Davis CM
FAU - Edin, Matthew L
AU  - Edin ML
FAU - Lee, Craig R
AU  - Lee CR
FAU - Zeldin, Darryl C
AU  - Zeldin DC
FAU - Alkayed, Nabil J
AU  - Alkayed NJ
LA  - eng
GR  - NS070837/NS/NINDS NIH HHS/United States
GR  - Z01 ES025034/ES/NIEHS NIH HHS/United States
GR  - R01 NS044313/NS/NINDS NIH HHS/United States
GR  - Z01 ES025034/ImNIH/Intramural NIH HHS/United States
GR  - R21 AG043857/AG/NIA NIH HHS/United States
GR  - R01 GM088199/GM/NIGMS NIH HHS/United States
GR  - T32 GM082770/GM/NIGMS NIH HHS/United States
GR  - P30 NS061800/NS/NINDS NIH HHS/United States
GR  - R01 NS070837/NS/NINDS NIH HHS/United States
GR  - T32 GM082770-03/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130409
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Vasodilator Agents)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Brain Ischemia/*enzymology/physiopathology
MH  - Cerebral Cortex/drug effects/*enzymology/physiopathology
MH  - Corpus Striatum/drug effects/*enzymology/physiopathology
MH  - Endothelium, Vascular/drug effects/*enzymology/physiopathology
MH  - Epoxide Hydrolases/blood/*genetics
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Sex Factors
MH  - Vasodilation
MH  - Vasodilator Agents/pharmacology
PMC - PMC3621731
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/04/16 06:00
MHDA- 2013/10/23 06:00
PMCR- 2013/04/09
CRDT- 2013/04/16 06:00
PHST- 2012/10/31 00:00 [received]
PHST- 2013/03/07 00:00 [accepted]
PHST- 2013/04/16 06:00 [entrez]
PHST- 2013/04/16 06:00 [pubmed]
PHST- 2013/10/23 06:00 [medline]
PHST- 2013/04/09 00:00 [pmc-release]
AID - PONE-D-12-34990 [pii]
AID - 10.1371/journal.pone.0061244 [doi]
PST - epublish
SO  - PLoS One. 2013 Apr 9;8(4):e61244. doi: 10.1371/journal.pone.0061244. Print 2013.