Epoxyeicosatrienoic Acid as Therapy for Diabetic and Ischemic Cardiomyopathy
| Autor: | John A. McClung, Nader G. Abraham, Mikhail Romashko, Joseph Schragenheim |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Diabetic Cardiomyopathies Vasodilator Agents Myocardial Ischemia Cardiomyopathy Inflammation Vasodilation 030204 cardiovascular system & hematology Pharmacology Toxicology Epoxyeicosatrienoic acid 03 medical and health sciences chemistry.chemical_compound 8 11 14-Eicosatrienoic Acid 0302 clinical medicine Downregulation and upregulation Internal medicine medicine Animals Humans Enzyme Inhibitors Endothelial dysfunction Epoxide Hydrolases Ischemic cardiomyopathy business.industry medicine.disease 030104 developmental biology Endocrinology Mechanism of action chemistry Cardiovascular Diseases Drug Design cardiovascular system lipids (amino acids peptides and proteins) Endothelium Vascular medicine.symptom business |
| Zdroj: | Trends in Pharmacological Sciences. 37:945-962 |
| ISSN: | 0165-6147 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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