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.