title: Epoxyeicosatrienoic acids and cardioprotection: the road to translation.
abstract: Cardiovascular disease, including acute myocardial infarction (AMI), is the leading cause of morbidity and mortality globally, despite well-established treatments. The discovery and development of novel therapeutics that prevent the progression of devastating consequences following AMI are thus important in reducing the global burden of this devastating disease. Scientific evidence for the protective effects of epoxyeicosatrienoic acids (EETs) in the cardiovascular system is rapidly emerging and suggests that promoting the effects of these cytochrome P450-derived epoxyeicosanoids is a potentially viable clinical therapeutic strategy. Through a translational lens, this review will provide insight into the potential clinical utility of this therapeutic strategy for AMI by 1) outlining the known cardioprotective effects of EETs and underlying mechanisms demonstrated in preclinical models of AMI with a particular focus on myocardial ischemia-reperfusion injury, 2) describing studies in human cohorts that demonstrate a relationship between EETs and associated pathways with coronary artery disease risk, and 3) discussing preclinical and clinical areas that require further investigation in order to increase the probability of successfully translating this rapidly emerging body of evidence into a clinically applicable therapeutic strategy for AMI.
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Center for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Akinyemi
authors.initials: A
authors.lastname: Oni-Orisan
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.
authors.forename: Nasser
authors.initials: N
authors.lastname: Alsaleh
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Center for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Lee
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada; Department of Pharmacology, University of Alberta, Edmonton, AB, Canada. Electronic address: jseubert@pharmacy.ualberta.ca.
authors.forename: John M
authors.initials: JM
authors.lastname: Seubert
mesh_terms: D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D015777:Eicosanoids / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D057285:Precision Medicine; D057170:Translational Research, Biomedical
chemical_list: D002316:Cardiotonic Agents; D015777:Eicosanoids; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases
keywords: Cardioprotection; Epoxyeicosatrienoic acid; Mitochondrial preservation; Myocardial ischemia–reperfusion injury; Personalized medicine; Soluble epoxide hydrolase