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 as a courtesy and upon agreement with Frontiers in Bioscience.


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
Academic Editor:Pin-Lan Li
Front. Biosci. (Landmark Ed) 2016, 21(7), 1427–1463;
Published: 1 June 2016
(This article belongs to the Special Issue Molecular pathobiology of lipid mediators)

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.

Cytochrome P450
Vascular Smooth Muscle
Endothelial Dysfunction
Vascular Remodeling
Vascular Inflammation
Ischemia Reperfusion
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