Soluble epoxide hydrolase and ischemic cardiomyopathy

Zhao, Tingting; Wasti, Binaya; Xu, Danyan; Shen, Li; Du, Jian-qing; Zhao, Shui‐Ping

doi:10.1016/j.ijcard.2011.05.067

Cited by 33 publications

(28 citation statements)

References 67 publications

(76 reference statements)

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“…Administration of sEHIs in multiple rodent and canine cardiac ischemia-reperfusion injury models prevented progressive cardiac remodeling and reduced infarct size in the heart (reviewed in 106, 115). Similar effects were observed in rodent stroke models (reviewed in 116), and the combination of sEHIs and EETs seems promising in this area in rodent and canine models (115, 117).…”

Section: Biological Effects Of Epoxy-fatty Acids and Soluble Epoxide mentioning

confidence: 99%

“…Similar effects were observed in rodent stroke models (reviewed in 116), and the combination of sEHIs and EETs seems promising in this area in rodent and canine models (115, 117). The R287N single-nucleotide polymorphism, which results in a low-sEH-activity phenotype, is associated with improved tolerance against ischemia (106), suggesting that in humans sEHIs have the potential to improve recovery from stroke and heart attacks.…”

Section: Biological Effects Of Epoxy-fatty Acids and Soluble Epoxide mentioning

confidence: 99%

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Impact of Soluble Epoxide Hydrolase and Epoxyeicosanoids on Human Health

Morisseau

Hammock

2013

Annu. Rev. Pharmacol. Toxicol.

475

495

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The presence of epoxyeicosatrienoic acids (EETs) in tissues and their metabolism by soluble epoxide hydrolase (sEH) to 1,2-diols were first reported 30 years ago. However, appreciation of their importance in cell biology and physiology has greatly accelerated over the past decade with the discovery of metabolically stable inhibitors of sEH, the commercial availability of EETs, and the development of analytical methods for the quantification of EETs and their diols. Numerous roles of EETs in regulatory biology now are clear, and the value of sEH inhibition in various animal models of disease has been demonstrated. Here, we review these results and discuss how the pharmacological stabilization of EETs and other natural epoxy-fatty acids could lead to possible disease therapies.

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Section: Biological Effects Of Epoxy-fatty Acids and Soluble Epoxide mentioning

confidence: 99%

Section: Biological Effects Of Epoxy-fatty Acids and Soluble Epoxide mentioning

confidence: 99%

Impact of Soluble Epoxide Hydrolase and Epoxyeicosanoids on Human Health

Morisseau

Hammock

2013

Annu. Rev. Pharmacol. Toxicol.

475

495

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“…Microsomal and soluble epoxide hyprolase are two wellknown epoxide hydrolase enzymes with different subcellular localization and substrate selectivity (24,47,128). The microsomal epoxide hydrolase is involved in the metabolism of environmental contaminants, whereas sEH was initially discovered as a metabolizing enzyme for carcinogenic xenobiotics until it was later found that sEH also metabolizes EETs to less active DHETs (69,73).…”

Section: Sehsmentioning

confidence: 99%

Reno-protective mechanisms of epoxyeicosatrienoic acids in cardiovascular disease

Elmarakby

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and it is well known that end-stage renal disease (ESRD) is a profound consequence of the progression of CVD. Present treatments only slow CVD progression to ESRD, and it is imperative that new therapeutic strategies are developed to prevent the incidence of ESRD. Because epoxyeicosatrienoic acids (EETs) have been shown to elicit reno-protective effects in hypertensive animal models, the current review will focus on addressing the reno-protective mechanisms of EETs in CVD. The cytochrome P-450 epoxygenase catalyzes the oxidation of arachidonic acid to EETs. EETs have been identified as endothelium-derived hyperpolarizing factors (EDHFs) with vasodilatory, anti-inflammatory, antihypertensive, and antiplatelet aggregation properties. EETs also have profound effects on vascular migration and proliferation and promote angiogenesis. The progression of CVD has been linked to decreased EETs levels, leading to the concept that EETs should be therapeutically targeted to prevent end-organ damage associated with CVD. However, EETs are quickly degraded by the enzyme soluble epoxide hydrolase (sEH) to their less active diols, dihydroxyeicosatrienoic acids (DHETs). As such, one way to increase EETs level is to inhibit their degradation to DHETs by using sEH inhibitors. Inhibition of sEH has been shown to effectively reduce blood pressure and organ damage in experimental models of CVD. Another approach to target EETs is to develop EET analogs with improved solubility and resistance to auto-oxidation and metabolism by sEH. For example, stable ether EET analogs dilate afferent arterioles and lower blood pressure in hypertensive rodent animal models. EET agonists also improve insulin signaling and vascular function in animal models of metabolic syndrome.

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“…In addition to being potentially involved in tissue inflammation, our study also suggests that the elevated EPHX2 expression may contribute to the delayed epithelium wound closure and sensory nerve regeneration in diabetic corneas. Most studies of EPHX2 focused on its effects on injuries associated with endothelia, including ischemic cardiomyopathy (43), vascular remodeling (44), and renal injury during diabetes (20), and associated with hypertension (28). The cornea is an avascular tissue, and as such, the effects of diabetes-induced upregulation on impaired wound healing are likely due to the direct effects on CECs.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Soluble Epoxide Hydrolase 2 Ameliorates Diabetic Keratopathy and Impaired Wound Healing in Mouse Corneas

et al. 2018

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EPHX2 (encoding soluble epoxide hydrolase [sEH]) converts biologically active epoxyeicosatrienoic acids (EETs), anti-inflammatory and profibrinolytic effectors, into the less biologically active metabolites, dihydroxyeicostrienoic acids. We sought to characterize the expression and the function of EPHX2 in diabetic corneas and during wound healing. The expression of EPHX2 at both mRNA and protein levels, as well as sEH enzymatic activity, was markedly upregulated in the tissues/cells, including corneal epithelial cells as well as the retina of human type 2 and mouse type 1 (streptozotocin [STZ] induced) and/or type 2 diabetes. depletion had no detectable effects on STZ-induced hyperglycemia but prevented the development of tear deficiency. mice showed an acceleration of hyperglycemia-delayed epithelium wound healing. Moreover, inhibition of sEH increased the rate of epithelium wound closure and restored hyperglycemia-suppressed STAT3 activation and heme oxygenase-1 (HO-1) expression in the diabetic corneas. Treatment of diabetic corneas with cobalt protoporphyrin, a well-known HO-1 inducer, restored wound-induced HO-1 upregulation and accelerated delayed wound healing. Finally, depletion enhanced sensory innervation and regeneration in diabetic corneas at 1 month after epithelial debridement. Our data suggest that increased sEH activity may be a contributing factor for diabetic corneal complications; targeting sEH pharmacologically or supplementing EETs may represent a new, adjunctive therapy for treating diabetic keratopathy.

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Soluble epoxide hydrolase and ischemic cardiomyopathy

Cited by 33 publications

References 67 publications

Impact of Soluble Epoxide Hydrolase and Epoxyeicosanoids on Human Health

Impact of Soluble Epoxide Hydrolase and Epoxyeicosanoids on Human Health

Reno-protective mechanisms of epoxyeicosatrienoic acids in cardiovascular disease

Inhibition of Soluble Epoxide Hydrolase 2 Ameliorates Diabetic Keratopathy and Impaired Wound Healing in Mouse Corneas

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