11,12-Epoxyeicosatrienoic acid (11,12-EET): structural determinants for inhibition of TNF-α-Induced VCAM-1 expression

Falck, John R.; Reddy, L. Manmohan; Reddy, Y. Krishna; Bondlela, Muralidhar; Krishna, U. Murali; Ji, Yu; Sun, Jianxin; Liao, James K.

doi:10.1016/j.bmcl.2003.08.060

Cited by 73 publications

(78 citation statements)

References 14 publications

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“…At nanomolar concentrations, the EETs, which are produced by the vascular endothelium, have a variety of antiinflammatory effects including inhibiting expression of several cell adhesion molecules and inhibiting leukocyte adhesion to the vascular wall (12,14,29). The data in this study can be interpreted in light of these hypothetical mechanisms of action.…”

Section: Discussionmentioning

confidence: 81%

Attenuation of tobacco smoke-induced lung inflammation by treatment with a soluble epoxide hydrolase inhibitor

Smith

Pinkerton

Watanabe

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

161

137

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Changes in the lungs due to smoking include inflammation, epithelial damage, and remodeling of the airways. Airway inflammation is likely to play a critical role in the genesis and progression of tobacco smoke-induced airway disease. Soluble epoxide hydrolase (sEH) is involved in the metabolism of endogenous chemical mediators that play an important role in inflammation. Epoxyeicosatrienoic acids (EETs) have demonstrated antiinflammatory properties, and hydrolysis of these epoxides by sEH is known to diminish this activity. To examine whether acute tobacco smokeinduced inflammation could be reduced by a sEH inhibitor, 12-(3-adamantane-1-yl-ureido)-dodecanoic acid n-butyl ester was given by daily s.c. injection to spontaneously hypertensive rats exposed to filtered air or tobacco smoke for a period of 3 days (6 h͞day). Acute exposure to tobacco smoke significantly increased by 3.2-fold (P < 0.05) the number of cells recovered by bronchoalveolar lavage. The sEH inhibitor significantly decreased total bronchoalveolar lavage cell number by 37% in tobacco smoke-exposed rats with significant reductions noted in neutrophils, alveolar macrophages, and lymphocytes. A combination of sEH inhibitor and EETs was more significant in its ability to further reduce tobacco smokeinduced inflammation compared with the sEH inhibitor alone. The sEH inhibitor led to a shift in some plasma epoxides and diols that are consistent with the hypothetical action of these compounds. We conclude that an sEH inhibitor, in the presence or absence of EETs, can attenuate, in part, inflammation associated with acute exposure to tobacco smoke. epoxyeicosatrienoic acids ͉ pulmonary ͉ antiinflammatory

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Section: Discussionmentioning

confidence: 81%

Attenuation of tobacco smoke-induced lung inflammation by treatment with a soluble epoxide hydrolase inhibitor

Smith

Pinkerton

Watanabe

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

161

137

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“…Node et al (78,79) provided the initial evidence that EETs possess anti-inflammatory properties. These investigators demonstrated that 11,12-EET inhibited TNF-␣-elicited expression of VCAM-1 and activation of NF-B (26,78,79). Overexpression of the epoxygenase CYP2J2 enzyme in endothelial cells also inhibited NF-B promoter activity (78).…”

Section: Epoxygenase Metabolites As An Edhf and Beyondmentioning

confidence: 96%

“…A couple of things that have remained elusive since the first biological actions of EETs were described: whether receptors for epoxygenase metabolites exist and how intracellular signaling events are triggered by EETs. In this regard, EET mimetics are already helping investigators to understand the structural activity requirements for biological activity (25,26). Identification of a binding site or receptor for EETs will undoubtedly open up new avenues for investigation.…”

Section: Renal and Cardiovascular Protective Actions Of Eets And Sehmentioning

confidence: 99%

Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal diseases

Imig¹

2005

American Journal of Physiology-Renal Physiology

210

246

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[775][776][777][778][779][780] 2003) have provided compelling evidence that cytochrome P-450-derived EETs have antihypertensive properties and are endothelially derived hyperpolarizing factors (EDHFs) in the kidney. EETs also possess anti-inflammatory actions that could protect the kidney vasculature from injury during renal and cardiovascular diseases. A tactic that has been used to increase EET levels has been inhibition of the soluble epoxide hydrolase enzyme. Epoxide hydrolase inhibitors have been demonstrated to be antihypertensive and renal protective. Thus the renal and cardiovascular protective actions of increasing epoxygenase levels could be translated to therapies for preventing end-organ damage. epoxyeicosatrienoic acids; endothelium-derived hyperpolarizing factor; hypertension; nephropathy; inflammation A MAJOR CAUSE OF MORBIDITY and mortality is the progression of organ damage associated with renal and cardiovascular diseases. For instance, the incidence of end-stage renal disease (ESRD) is escalating and the number of patients on dialysis is predicted to double over the 10-yr period of 2000 -2010 (7, 9, 19, 34, 104). The two main diseases responsible for the increase in ESRD are diabetes and hypertension. One contributing factor to end-organ damage is an impaired endothelium (6,21,56,60,95). Interestingly, endothelial dysfunction has recently been touted as a marker for unfavorable cardiovascular prognosis in humans (5,27,66). Others and we have established that cytochrome P-450 (CYP) metabolites (CYP2C) produced by the endothelium have antihypertensive properties and proposed that the epoxyeicosatrienoic acids (EETs) are endothelium-derived hyperpolarizing factors (EDHFs) (2,12,30,43,50,87). Additionally, EETs have profibrinolytic effects, anti-inflammatory actions, and inhibit smooth vascular muscle cell migration (11,20,32,78,79,94). Recent interest has also focused on the role of soluble epoxide hydrolase (SEH) in renal and cardiovascular disease and inhibition of this enzyme as an avenue to increase EET levels. This review will highlight these favorable EET properties that could protect the kidney from ESRD during renal and cardiovascular disease states. EPOXYGENASE METABOLITES AS AN EDHF AND BEYONDThe contribution of the endothelial cells to the control of blood flow has been recognized for over two decades. Earlier studies established that endothelium-derived factors could act on vascular smooth muscle cells to relax or contract arteries (38,68). The identity of nitric oxide and prostaglandins as the main products of the endothelial cells that relax the vascular smooth muscle has been well established (10,38,67,68). In addition, the fact that the endothelium released one or more substances that relaxed vascular smooth muscle cells through membrane hyperpolarization was also repeatedly demonstrated (10,67,95). A number of studies have provided evidence that this nitric oxide-and cyclooxygenase (COX)-independent endothelium-derived relaxing factor was a metabolite of the arachidonic acid c...

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“…Despite the fact that more studies are needed to resolve the precise cellular signalling mechanisms involved in the anti‐inflammatory actions of EETs, there is great evidence that EETs reduce inflammation. It is suggested that EETs inhibit the stimulation of the transcription factor nuclear factor to produce their vascular anti‐inflammatory responses 15, 16. Studies using inhibitors of soluble epoxide hydrolase (sEH) also support the idea that EETs have anti‐inflammatory actions 17, 18.…”

Section: Discussionmentioning

confidence: 99%

11,12-Epoxyeicosatrienoic acid induces vasodilator response in the rat perfused mesenteric vasculature

Bihzad

Yousif

2017

Auton Autacoid Pharmacol

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Summary Epoxyeicosatrienoic acids (EETs) are endogenous ligands that undergo hydrolysis by soluble epoxide hydrolase (sEH). The responses of 11, 12‐EET in comparison with other vasodilator agonists including carbachol and sodium nitroprusside (SNP) were investigated. The effect of 1‐cyclohexyl‐3‐dodecyl urea (CDU), a sEH, was tested on the vasodilator effect induced by 11, 12‐EET in the perfused mesenteric beds isolated from normo‐glycaemic and type‐1 STZ‐diabetic rats.In the perfused mesenteric beds of control and diabetic animals, 11, 12‐EET produced vasodilation in a dose‐dependent manner. The vasodilator response induced by 11, 12‐EET was significantly decreased in tissues obtained from diabetic animals, but this was significantly corrected through inhibition of sEH.The effects of nitric oxide synthase inhibitor, cyclo‐oxygenase inhibitor, specific potassium channel inhibitors, soluble guanylyl cyclase inhibitor and transient receptor potential channel V4 inhibitor, on vasodilator response to 11, 12‐EET were investigated.In tissues isolated from control animals, vasodilator responses to 11, 12‐EET were not inhibited by acute incubation with l‐NAME, l‐NAME with indomethacin, glibenclamide, iberiotoxin, charybdotoxin, apamin or ODQ.Incubation with the transient receptor potential channel V4 inhibitor ruthenium red caused significantly reduced vasodilator responses induced by 11, 12‐EET.In conclusion, results from this study indicate that 11, 12‐EET has a vasodilator effect in the perfused mesenteric bed, partly through activation of vanilloid receptor. A strategy to elevate the levels of EETs may have a significant impact in correcting microvascular abnormality associated with diabetes.

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11,12-Epoxyeicosatrienoic acid (11,12-EET): structural determinants for inhibition of TNF-α-Induced VCAM-1 expression

Cited by 73 publications

References 14 publications

Attenuation of tobacco smoke-induced lung inflammation by treatment with a soluble epoxide hydrolase inhibitor

Attenuation of tobacco smoke-induced lung inflammation by treatment with a soluble epoxide hydrolase inhibitor

Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal diseases

11,12-Epoxyeicosatrienoic acid induces vasodilator response in the rat perfused mesenteric vasculature

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