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

Front Biosci (Landmark Ed). 2016 Jun 1;21(7):1427-63. doi: 10.2741/4465.

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.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Vessels / physiopathology*
  • Brain Injuries, Traumatic / physiopathology
  • Endothelium, Vascular / physiology
  • Humans
  • Hydroxyeicosatetraenoic Acids / physiology*
  • Muscle, Smooth, Vascular / physiology
  • Neovascularization, Physiologic
  • Platelet Aggregation / physiology
  • Reperfusion Injury / physiopathology
  • Signal Transduction
  • Stroke / physiopathology
  • Subarachnoid Hemorrhage / physiopathology
  • Vasculitis / physiopathology

Substances

  • Hydroxyeicosatetraenoic Acids
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid