scholarly journals GENETIC DELETION OF SOLUBLE EPOXIDE HYDROLASE PRESERVES CARDIAC FUNCTION IN AGED FEMALE MICE

2019 ◽  
Vol 35 (10) ◽  
pp. S12
Author(s):  
H. Keshavarz-Bahaghighat ◽  
K. Jamieson ◽  
A. Darwesh ◽  
J. Seubert
Keyword(s):  
Cardiac Function ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Female Mice ◽  
Genetic Deletion

scholarly journals Soluble Epoxide Hydrolase in Aged Female Mice and Human Explanted Hearts Following Ischemic Injury

2021 ◽  
Vol 22 (4) ◽  
pp. 1691
Author(s):  
K. Lockhart Jamieson ◽  
Ahmed M. Darwesh ◽  
Deanna K. Sosnowski ◽  
Hao Zhang ◽  
Saumya Shah ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Epoxide Hydrolase ◽  
Significant Proportion ◽  
Ischemic Injury ◽  
Soluble Epoxide Hydrolase ◽  
Mitochondrial Activity ◽  
Metabolite Formation ◽  
Female Mice ◽  
Enzymatic Function

Myocardial infarction (MI) accounts for a significant proportion of death and morbidity in aged individuals. The risk for MI in females increases as they enter the peri-menopausal period, generally occurring in middle-age. Cytochrome (CYP) 450 metabolizes N-3 and N-6 polyunsaturated fatty acids (PUFA) into numerous lipid mediators, oxylipids, which are further metabolised by soluble epoxide hydrolase (sEH), reducing their activity. The objective of this study was to characterize oxylipid metabolism in the left ventricle (LV) following ischemic injury in females. Human LV specimens were procured from female patients with ischemic cardiomyopathy (ICM) or non-failing controls (NFC). Female C57BL6 (WT) and sEH null mice averaging 13–16 months old underwent permanent occlusion of the left anterior descending coronary artery (LAD) to induce myocardial infarction. WT (wild type) mice received vehicle or sEH inhibitor, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (tAUCB), in their drinking water ad libitum for 28 days. Cardiac function was assessed using echocardiography and electrocardiogram. Protein expression was determined using immunoblotting, mitochondrial activity by spectrophotometry, and cardiac fibre respiration was measured using a Clark-type electrode. A full metabolite profile was determined by LC–MS/MS. sEH was significantly elevated in ischemic LV specimens from patients, associated with fundamental changes in oxylipid metabolite formation and significant decreases in mitochondrial enzymatic function. In mice, pre-treatment with tAUCB or genetic deletion of sEH significantly improved survival, preserved cardiac function, and maintained mitochondrial quality following MI in female mice. These data indicate that sEH may be a relevant pharmacologic target for women with MI. Although future studies are needed to determine the mechanisms, in this pilot study we suggest targeting sEH may be an effective strategy for reducing ischemic injury and mortality in middle-aged females.

scholarly journals Genetic deletion of soluble epoxide hydrolase preserves cardiac function and limits inflammation in acute lipopolysaccharide injury

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Deanna Sosnowski ◽  
K. Jamieson ◽  
Ahmed Darwesh ◽  
Artiom Gruzdev ◽  
Darryl Zeldin ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Genetic Deletion

scholarly journals Differential effects of soluble epoxide hydrolase inhibition and CYP2J2 overexpression on postischemic cardiac function in aged mice

2013 ◽  
Vol 104-105 ◽  
pp. 8-17 ◽  
Author(s):  
Ketul R. Chaudhary ◽  
Beshay N.M. Zordoky ◽  
Matthew L. Edin ◽  
Nasser Alsaleh ◽  
Ayman O.S. El-Kadi ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Differential Effects ◽  
Aged Mice

scholarly journals Soluble Epoxide Hydrolase Deletion Limits High-Fat Diet-Induced Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Karen M. Wagner ◽  
Jun Yang ◽  
Christophe Morisseau ◽  
Bruce D. Hammock
Keyword(s):  
Fatty Acids ◽  
High Fat Diet ◽  
Epoxide Hydrolase ◽  
Biological Effects ◽  
Soluble Epoxide Hydrolase ◽  
Bioactive Lipids ◽  
High Fat ◽  
Female Mice ◽  
Epoxy Fatty Acids ◽  
Fat Diets

The soluble epoxide hydrolase (sEH) enzyme is a major regulator of bioactive lipids. The enzyme is highly expressed in liver and kidney and modulates levels of endogenous epoxy-fatty acids, which have pleiotropic biological effects including limiting inflammation, neuroinflammation, and hypertension. It has been hypothesized that inhibiting sEH has beneficial effects on limiting obesity and metabolic disease as well. There is a body of literature published on these effects, but typically only male subjects have been included. Here, we investigate the role of sEH in both male and female mice and use a global sEH knockout mouse model to compare the effects of diet and diet-induced obesity. The results demonstrate that sEH activity in the liver is modulated by high-fat diets more in male than in female mice. In addition, we characterized the sEH activity in high fat content tissues and demonstrated the influence of diet on levels of bioactive epoxy-fatty acids. The sEH KO animals had generally increased epoxy-fatty acids compared to wild-type mice but gained less body weight on higher-fat diets. Generally, proinflammatory prostaglandins and triglycerides were also lower in livers of sEH KO mice fed HFD. Thus, sEH activity, prostaglandins, and triglycerides increase in male mice on high-fat diet but are all limited by sEH ablation. Additionally, these changes also occur in female mice though at a different magnitude and are also improved by knockout of the sEH enzyme.

scholarly journals Deficiency of Soluble Epoxide Hydrolase Protects Cardiac Function Impaired by LPS-Induced Acute Inflammation

2019 ◽  
Vol 9 ◽  
Author(s):  
Victor Samokhvalov ◽  
K. Lockhart Jamieson ◽  
Ahmed M. Darwesh ◽  
Hedieh Keshavarz-Bahaghighat ◽  
Tim Y. T. Lee ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Epoxide Hydrolase ◽  
Acute Inflammation ◽  
Soluble Epoxide Hydrolase

scholarly journals Pharmacological inhibition of soluble epoxide hydrolase or genetic deletion reduces diclofenac-induced gastric ulcers

Life Sciences ◽  
2017 ◽  
Vol 180 ◽  
pp. 114-122 ◽  
Author(s):  
Sumanta Kumar Goswami ◽  
Amelia Ann Rand ◽  
Debin Wan ◽  
Jun Yang ◽  
Bora Inceoglu ◽  
...  
Keyword(s):  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Gastric Ulcers ◽  
Pharmacological Inhibition ◽  
Genetic Deletion

Genetic deletion of soluble epoxide hydrolase provides cardioprotective responses following myocardial infarction in aged mice

2017 ◽  
Vol 132 ◽  
pp. 47-58 ◽  
Author(s):  
K. Lockhart Jamieson ◽  
Victor Samokhvalov ◽  
Maria K. Akhnokh ◽  
Kyra Lee ◽  
Woo Jung Cho ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Aged Mice ◽  
Genetic Deletion
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