Victor Garcia1, Michal L Schwartzman. 1. aDepartment of Pharmacology, Yale University, New Haven, Connecticut bDepartment of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA.
Abstract
PURPOSE OF REVIEW: 20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoactive eicosanoid and a key constituent of the microcirculation. Its effects on vascular function are multifaceted and include stimulation of smooth muscle, contractility, migration, and proliferation, as well as endothelial cell dysfunction and inflammation. Such effects have significant implications with regard to the control of vascular homeostasis and pathophysiology. The clinical relevance of 20-HETE is highlighted by recent studies linking 20-HETE and its biosynthetic enzymes to the development of hypertension, stroke, and myocardial infarction. RECENT FINDINGS: This article presents past and recent findings that focus on the role of 20-HETE in the regulation of the vasculature in health and disease and the implication of its actions on endothelial and vascular smooth muscle cells to the pathogenesis of hypertension and stroke. SUMMARY: To date clinical studies corroborated animal studies in that they place 20-HETE as a significant contributor to the pathogenesis of cardiovascular diseases. Consequently, uncovering 20-HETE effects in the vasculature along with understanding its mechanism of action provide a strong basis for the development of novel therapeutic strategies to prevent vascular/end organ damage in these diseases.
PURPOSE OF REVIEW: 20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoactive eicosanoid and a key constituent of the microcirculation. Its effects on vascular function are multifaceted and include stimulation of smooth muscle, contractility, migration, and proliferation, as well as endothelial cell dysfunction and inflammation. Such effects have significant implications with regard to the control of vascular homeostasis and pathophysiology. The clinical relevance of 20-HETE is highlighted by recent studies linking 20-HETE and its biosynthetic enzymes to the development of hypertension, stroke, and myocardial infarction. RECENT FINDINGS: This article presents past and recent findings that focus on the role of 20-HETE in the regulation of the vasculature in health and disease and the implication of its actions on endothelial and vascular smooth muscle cells to the pathogenesis of hypertension and stroke. SUMMARY: To date clinical studies corroborated animal studies in that they place 20-HETE as a significant contributor to the pathogenesis of cardiovascular diseases. Consequently, uncovering 20-HETE effects in the vasculature along with understanding its mechanism of action provide a strong basis for the development of novel therapeutic strategies to prevent vascular/end organ damage in these diseases.
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Authors: Ankit Gilani; Varunkumar Pandey; Victor Garcia; Kevin Agostinucci; Shailendra P Singh; Joseph Schragenheim; Lars Bellner; John R Falck; Mahesh P Paudyal; Jorge H Capdevila; Nader G Abraham; Michal Laniado Schwartzman Journal: Am J Physiol Regul Integr Comp Physiol Date: 2018-08-08 Impact factor: 3.619