title: 20-Hydroxyeicosatetraenoic acid is a potential therapeutic target in cardiovascular diseases.
abstract: Arachidonic acid (AA) is metabolized by enzymes of the cytochrome P450 (CYP) 4A and CYP4F subfamilies to 20- hydroxyeicosatetraeonic acid (20-HETE), which plays an important role in the cardiovascular system. In the current work, we reviewed the formation of 20-HETE in different species by different CYPs; 20-HETE metabolism by cyclooxygenases (COXs) and different isomerases; and the current available inducers and inhibitors of 20-HETE formation in addition to its agonists and antagonists. Moreover we reviewed the negative role of 20-HETE in cardiac hypertrophy, cardiotoxicity, diabetic cardiomyopathy, and in ischemia/reperfusion (I/R) injury. Lastly, we reviewed the role of 20-HETE in different hypertension models such as the renin/angiotensin II model, Goldblatt model, spontaneously hypertensive rat model, androgen-induced model, slat- and deoxycorticosterone acetate (DOCA)-salt-induced models, and high fat diet model. 20-HETE can affect pro- and anti-hypertensive mechanisms dependent upon where, when, and by which isoform it has been produced. In contrast to hypertension we also reviewed the role of 20-HETE in endotoxin-induced hypotension and the natriuretic effects of 20-HETE. Based on the recent studies, 20-HETE production and/or action might be a therapeutic target to protect against the initiation and progression of cardiovascular diseases.
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Osama H
authors.initials: OH
authors.lastname: Elshenawy
authors.forename: Anwar
authors.initials: A
authors.lastname: Anwar-Mohamed
authors.forename: Ayman O S
authors.initials: AO
authors.lastname: El-Kadi
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D006900:Hydroxylation
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid