Title:20-Hydroxyeicosatetraenoic Acid is a Potential Therapeutic Target in Cardiovascular Diseases
VOLUME: 14 ISSUE: 6
Author(s):Osama H. Elshenawy, Anwar Anwar-Mohamed and Ayman O.S. El-Kadi
Affiliation:Faculty of Pharmacy & Pharmaceutical Sciences, 2142J Katz Group-Rexall Centre for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta, Canada T6G 2E1.
Keywords:Cytochrome P450s (CYPs), 20-hydroxyeicosatetraeonic acid (20-HETE), Arachidonic acid (AA), 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.
