The role of 20-HETE in cardiovascular diseases and its risk factors.
Arachidonic acid (AA) is metabolized in mammals by enzymes of the CYP4A and 4F families to 20-hydroxyeicosatetraeonic acid (20-HETE) which plays an important role in the regulation of renal function, vascular tone and arterial pressure. In the vasculature, 20-HETE is a potent vasoconstrictor, the up-regulation of which contributes to inflammation, oxidative stress, endothelial dysfunction and an increase in peripheral vascular resistance in models of obesity, diabetes, ischemia/reperfusion, and vascular oxidative stress. Recent studies have established a role for 20-HETE in normal and pathological angiogenic conditions. We discuss in this review the synthesis of 20-HETE and how it and various autacoids, especially the renin-angiotensin system, interact to promote hypertension, vasoconstriction, and vascular dysfunction. In addition, we examine the molecular mechanisms through which 20-HETE induces these actions and the clinical implication of inhibiting 20-HETE production and activity.
Cardiac Research Laboratory, Felsenstein Medical Research Center, Petah Tikva and Sackler School of Medicine, Tel Aviv University, Israel; Leviev Heart Center, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University, Israel.
Maayan
M
Waldman
Department of Medicine, New York Methodist Hospital, Brooklyn, NY 11215, United States.
Stephen J
SJ
Peterson
Leviev Heart Center, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University, Israel.
Michael
M
Arad
Cardiac Research Laboratory, Felsenstein Medical Research Center, Petah Tikva and Sackler School of Medicine, Tel Aviv University, Israel. Electronic address: hochhaus@post.tau.ac.il.
Edith
E
Hochhauser
D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D005355:Fibrosis; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis / Q000378:metabolism*; D012307:Risk Factors
D006893:Hydroxyeicosatetraenoic Acids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid
20-HETE; Cardiovascular disease (CVD); Diabetes; Obesity