IMR Press / FBL / Volume 21 / Issue 7 / DOI: 10.2741/4465

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Review

Molecular mechanisms and cell signaling of 20-hydroxyeicosatetraenoic acid in vascular pathophysiology

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1 Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA
2 Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, Qingdao, China
3 Department of General Medicine and Rehabilitation, Tohoku Medical and Pharmaceutical University School of Medicine, Sendai, Japan
4 Taisho Pharmaceutical Co., Ltd., Saitama, Japan
Front. Biosci. (Landmark Ed) 2016, 21(7), 1427–1463; https://doi.org/10.2741/4465
Published: 1 June 2016
Abstract

Cytochrome P450s enzymes catalyze the metabolism of arachidonic acid to epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid and hydroxyeicosatetraeonic acid (HETEs). 20-HETE is a vasoconstrictor that depolarizes vascular smooth muscle cells by blocking K+ channels. EETs serve as endothelial derived hyperpolarizing factors. Inhibition of the formation of 20-HETE impairs the myogenic response and autoregulation of renal and cerebral blood flow. Changes in the formation of EETs and 20-HETE have been reported in hypertension and drugs that target these pathways alter blood pressure in animal models. Sequence variants in CYP4A11 and CYP4F2 that produce 20-HETE, UDP-glucuronosyl transferase involved in the biotransformation of 20-HETE and soluble epoxide hydrolase that inactivates EETs are associated with hypertension in human studies. 20-HETE contributes to the regulation of vascular hypertrophy, restenosis, angiogenesis and inflammation. It also promotes endothelial dysfunction and contributes to cerebral vasospasm and ischemia-reperfusion injury in the brain, kidney and heart. This review will focus on the role of 20-HETE in vascular dysfunction, inflammation, ischemic and hemorrhagic stroke and cardiac and renal ischemia reperfusion injury.

Keywords
20-HETE
Cytochrome P450
Vascular Smooth Muscle
Endothelial Dysfunction
Vascular Remodeling
Vascular Inflammation
Ischemia Reperfusion
Stroke
Review
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