scholarly journals Soluble Epoxide Hydrolase Gene Deletion Is Protective Against Experimental Cerebral Ischemia

Stroke ◽  
2008 ◽  
Vol 39 (7) ◽  
pp. 2073-2078 ◽  
Author(s):  
Wenri Zhang ◽  
Takashi Otsuka ◽  
Nobuo Sugo ◽  
Ardi Ardeshiri ◽  
Yazan K. Alhadid ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Epoxide Hydrolase ◽  
Gene Deletion ◽  
Soluble Epoxide Hydrolase ◽  
Experimental Cerebral Ischemia

scholarly journals Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation

Resuscitation ◽  
2008 ◽  
Vol 76 (1) ◽  
pp. 89-94 ◽  
Author(s):  
Michael P. Hutchens ◽  
Takaaki Nakano ◽  
Jennifer Dunlap ◽  
Richard J. Traystman ◽  
Patricia D. Hurn ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Epoxide Hydrolase ◽  
Gene Deletion ◽  
Soluble Epoxide Hydrolase

Soluble epoxide hydrolase gene deletion reduces inflammation after stroke

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S93-S93
Author(s):  
Ines P Koerner ◽  
Wenri Zhang ◽  
Patricia D Hurn ◽  
Dennis Koop ◽  
Nabil J Alkayed
Keyword(s):  
Epoxide Hydrolase ◽  
Gene Deletion ◽  
Soluble Epoxide Hydrolase

scholarly journals Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension

2009 ◽  
Vol 297 (3) ◽  
pp. F740-F748 ◽  
Author(s):  
Marlina Manhiani ◽  
Jeffrey E. Quigley ◽  
Sarah F. Knight ◽  
Shiva Tasoobshirazi ◽  
TarRhonda Moore ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Epoxide Hydrolase ◽  
Gene Deletion ◽  
Soluble Epoxide Hydrolase ◽  
Glomerular Injury ◽  
Renal Protection ◽  
Renal Inflammation ◽  
Arterial Blood ◽  
Salt Hypertension ◽  
Salt Sensitive Hypertension

Inhibition of soluble epoxide hydrolase (sEH) has been shown to be renal protective in rat models of salt-sensitive hypertension. Here, we hypothesize that targeted disruption of the sEH gene (Ephx2) prevents both renal inflammation and injury in deoxycorticosterone acetate plus high salt (DOCA-salt) hypertensive mice. Mean arterial blood pressure (MAP) increased significantly in the DOCA-salt groups, and MAP was lower in Ephx2−/− DOCA-salt (129 ± 3 mmHg) compared with wild-type (WT) DOCA-salt (145 ± 2 mmHg) mice. Following 21 days of treatment, WT DOCA-salt urinary MCP-1 excretion increased from control and was attenuated in the Ephx2−/− DOCA-salt group. Macrophage infiltration was reduced in Ephx2−/− DOCA-salt compared with WT DOCA-salt mice. Albuminuria increased in WT DOCA-salt (278 ± 55 μg/day) compared with control (17 ± 1 μg/day) and was blunted in the Ephx2−/− DOCA-salt mice (97 ± 23 μg/day). Glomerular nephrin expression demonstrated an inverse relationship with albuminuria. Nephrin immunofluorescence was greater in the Ephx2−/− DOCA-salt group (3.4 ± 0.3 RFU) compared with WT DOCA-salt group (1.1 ± 0.07 RFU). Reduction in renal inflammation and injury was also seen in WT DOCA-salt mice treated with a sEH inhibitor { trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid; tAUCB}, demonstrating that the C-terminal hydrolase domain of the sEH enzyme is responsible for renal protection with DOCA-salt hypertension. These data demonstrate that Ephx2 gene deletion decreases blood pressure, attenuates renal inflammation, and ameliorates glomerular injury in DOCA-salt hypertension.

scholarly journals Role of Soluble Epoxide Hydrolase in the Sex-Specific Vascular Response to Cerebral Ischemia

2009 ◽  
Vol 29 (8) ◽  
pp. 1475-1481 ◽  
Author(s):  
Wenri Zhang ◽  
Jeffrey J Iliff ◽  
Caitlyn J Campbell ◽  
Ruikang K Wang ◽  
Patricia D Hurn ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Epoxide Hydrolase ◽  
Focal Cerebral Ischemia ◽  
Soluble Epoxide Hydrolase ◽  
Artery Occlusion ◽  
Male Mice ◽  
Key Enzyme

Soluble epoxide hydrolase (sEH), a key enzyme in the metabolism of vasodilator eicosanoids called epoxyeicosatrienoic acids (EETs), is sexually dimorphic and suppressed by estrogen. We determined if the sex difference in blood flow during focal cerebral ischemia is linked to sEH. Soluble epoxide hydrolase expression in brain, hydrolase activity in cerebral vessels, and plasma 14,15-dihydroxyeicosatrienoic acid (14,15-DHET) were determined in male and female wild-type (WT) and sEH knockout (sEHKO) mice. Male, female, and ovariectomized female WT and sEHKO mice were subjected to 2-h middle cerebral artery occlusion (MCAO) and infarct size was measured at 24 h of reperfusion. Laser—Doppler cortical perfusion during MCAO was compared among groups and differences in cortical blood flow rates were confirmed using in vivo quantitative optical microangiography. Cerebrovascular expression and activity of sEH and plasma 14,15-DHET were lower in WT female than male mice, and blood flow during MCAO was higher and infarct size was smaller in WT female compared with male mice. Sex differences in cerebral blood flow and ischemic damage were abolished after ovariectomy and were absent in sEHKO mice. We conclude that sEH is an important mechanism underlying sex-linked differences in blood flow and brain damage after cerebral ischemia.

scholarly journals Soluble epoxide hydrolase inhibition decreases reperfusion injury after focal cerebral ischemia

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ranran Tu ◽  
Jillian Armstrong ◽  
Kin Sing Stephen Lee ◽  
Bruce D. Hammock ◽  
Adam Sapirstein ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Epoxide Hydrolase ◽  
Focal Cerebral Ischemia ◽  
Soluble Epoxide Hydrolase

scholarly journals Soluble epoxide hydrolase inhibition modulates vascular remodeling

2010 ◽  
Vol 298 (3) ◽  
pp. H795-H806 ◽  
Author(s):  
A. N. Simpkins ◽  
R. D. Rudic ◽  
S. Roy ◽  
H. J. Tsai ◽  
B. D. Hammock ◽  
...  
Keyword(s):  
Vascular Injury ◽  
Vascular Remodeling ◽  
Epoxide Hydrolase ◽  
Gene Deletion ◽  
Therapeutic Potential ◽  
Soluble Epoxide Hydrolase ◽  
Dodecanoic Acid ◽  
Neointimal Formation ◽  
Carotid Ligation

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.

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