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

Fan Fan, Ying Ge, Wenshan Lv, Matthew R. Elliott, Yoshikazu Muroya, Takashi Hirata, George W. Booz, Richard J. Roman

Research output: Contribution to journalReview articlepeer-review

73 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1427-1463
Number of pages37
JournalFrontiers in Bioscience - Landmark
Volume21
Issue number7
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Keywords

  • 20-HETE
  • Cytochrome P450
  • Endothelial dysfunction
  • Ischemia reperfusion
  • Review
  • Stroke
  • Vascular inflammation
  • Vascular remodeling
  • Vascular smooth muscle

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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