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

Chaudhary, Ketul R; Zordoky, Beshay N.; Edin, Matthew L.; Alsaleh, Nasser B.; El‐Kadi, Ayman O.S.; Zeldin, Darryl C.; Seubert, John M.

doi:10.1016/j.prostaglandins.2012.08.001

Cited by 39 publications

(36 citation statements)

References 46 publications

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“…Previous studies have shown that increasing the EETs bioavailability by using AUDA, a sEH inhibitor, improves cardiac hypertrophy and cardiac injury and perfusion . The beneficial cardiac protective effects of EETs were abolished by MSPPOH, an inhibitor of EET‐synthesizing enzyme . The observed cardiac protective effect of fenofibrate in our study may have occurred due to enhanced production of endogenous EETs .…”

Section: Discussionsupporting

confidence: 59%

Protective effect of fenofibrate against ischemia‐/reperfusion‐induced cardiac arrhythmias in isolated rat hearts

Bukhari

Almotrefi

Mohamed

et al. 2018

Fundamemntal Clinical Pharma

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Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α activator that lowers triglycerides and influences cytochrome P-450 (CYP-450) epoxygenase-dependent arachidonic acid (AA) metabolism. CYP-450 epoxygenase metabolizes AA to epoxyeicosatrienoic acids (EETs). EETs have coronary dilating and cardiac and renal protective properties. Fibrates possess similar properties due to their CYP-450 epoxygenase-inducing properties that lead to increase in endogenous EET production. In the current investigations, fenofibrate (100 mg/kg, orally) for 2 weeks decreased ischemia-/reperfusion (I/R)-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) in the isolated rat hearts. Fenofibrate caused marked inhibition of the reperfusion-induced cardiac arrhythmias. The incidence of reperfusion-induced VF decreased from 80% in the control vehicle-treated animals to 33% in the fenofibrate-treated animals (P < 0.001). PVCs were also significantly (P < 0.01) decreased from 223.2 ± 51 in control vehicle-treated animals to 136.8 ± 22 in fenofibrate-treated animals. Total duration of reperfusion-induced VT decreased from 29.2 ± 6.3 s in control, vehicle-treated animals to 4.8 ± 1.3 s in fenofibrate-treated animals, P < 0.001. Heart rate and perfusion pressure were not significantly affected by fenofibrate pretreatment. Diltiazem, a clinically used anti-arrhythmic agent, produced complete protection against I/R-induced cardiac arrhythmias in this model reducing the incidence of VF from 80% in control, vehicle-treated animals to 10% in diltiazem-treated hearts. These findings indicate that fenofibrate suppresses arrhythmias in isolated rat hearts subjected to I/R-induced injury.

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Section: Discussionsupporting

confidence: 59%

Protective effect of fenofibrate against ischemia‐/reperfusion‐induced cardiac arrhythmias in isolated rat hearts

Bukhari

Almotrefi

Mohamed

et al. 2018

Fundamemntal Clinical Pharma

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“…When isolated hearts in a Langendorff apparatus are subjected to ischemia and reflow, hearts from sEH null mice display enhanced recovery of left ventricular developed pressure compared to controls (Seubert et al, 2006; Chaudhary et al, 2012). In an in vivo model where the left coronary artery was surgically occluded and then released from its snare to allow reperfusion, the infarction area was reduced in sEH null animals, indicating reduced injury (Motoki et al, 2008).…”

Section: Seh Genetic Modelsmentioning

confidence: 99%

Soluble epoxide hydrolase: Gene structure, expression and deletion

Harris

Hammock

2013

Gene

192

184

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Mammalian soluble epoxide hydrolase (sEH) converts epoxides to their corresponding diols through the addition of a water molecule. sEH readily hydrolyzes lipid signaling molecules, including the epoxyeicosatrienoic acids (EETs), epoxidized lipids produced from arachidonic acid by the action of cytochrome p450s. Through its metabolism of the EETs and other lipid mediators, sEH contributes to the regulation of vascular tone, nociception, angiogenesis and the inflammatory response. Because of its central physiological role in disease states such as cardiac hypertrophy, diabetes, hypertension, and pain sEH is being investigated as a therapeutic target. This review begins with a brief introduction to sEH protein structure and function. sEH evolution and gene structure are then discussed before human small nucleotide polymorphisms and mammalian gene expression are described in the context of several disease models. The review ends with an overview of studies that have employed the sEH knockout mouse model.

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“…Because protection was recovered after the administration of an sEH inhibitor, the loss of protection may have been related to an age-related increase in the expression of the sEH or the accumulation of a cardiotoxic metabolite. The latter seemed to be the case because the older transgenic animals demonstrated increased levels of 9,10-DiHOME, which was accompanied by increased oxidative stress (Chaudhary et al, 2013b). Whether levels of CYP2C epoxygenases were increased in the affected animals was not determined.…”

Section: B Cytochrome P450-derived Mediators In the Heartmentioning

confidence: 99%

The Pharmacology of the Cytochrome P450 Epoxygenase/Soluble Epoxide Hydrolase Axis in the Vasculature and Cardiovascular Disease

2014

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

Cited by 39 publications

References 46 publications

Protective effect of fenofibrate against ischemia‐/reperfusion‐induced cardiac arrhythmias in isolated rat hearts

Protective effect of fenofibrate against ischemia‐/reperfusion‐induced cardiac arrhythmias in isolated rat hearts

Soluble epoxide hydrolase: Gene structure, expression and deletion

The Pharmacology of the Cytochrome P450 Epoxygenase/Soluble Epoxide Hydrolase Axis in the Vasculature and Cardiovascular Disease

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