title: Epoxyeicosatrienoic Acid as Therapy for Diabetic and Ischemic Cardiomyopathy.
abstract: Cardiovascular disease remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves epoxyeicosatrienoic acid (EET) and soluble epoxide hydroxylase (sEH) inhibition. sEH is the enzyme that converts EET to its less potent metabolite; therefore, EET is upregulated by its inhibitor. EET has pleotropic effects that collectively reduce inflammation, while increasing vasodilation and insulin sensitivity. Recent reports indicate that EET agonists and sEH inhibitors are capable of not only reversing endothelial dysfunction and hypertension, but also of reversing cardiac remodeling, which is a hallmark of cardiomyopathy and the metabolic syndrome. EET agonists and sEH inhibitors are in development as potential therapies, and at least one drug is already in clinical trials. This review examines the activity of EET in biological systems, proposes a series of pathways to explain its mechanism of action, and discusses how these might be exploited for potential therapeutic use.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Romashko
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Schragenheim
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA; Department of Medicine, New York Medical College, Valhalla, NY 10595, USA; Department of Pharmacology and Medicine, Joan C. Edwards School of Medicine, Huntington, WV 25701, USA.
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
authors.affiliation: Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. Electronic address: John.McClungMD@wmchealth.org.
authors.forename: John A
authors.initials: JA
authors.lastname: McClung
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy / Q000503:physiopathology; D015195:Drug Design; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D004851:Epoxide Hydrolases; D015126:8,11,14-Eicosatrienoic Acid
keywords: HO-1; PGC-1α; diabetes mellitus; epoxyeicosatrienoic acid (EET); heart failure; metabolic syndrome