1. Molecular mechanisms and cell signaling of 20-hydroxyeicosatetraenoic acid in vascular pathophysiology
- Author
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Yoshikazu Muroya, Richard J. Roman, Matthew R Elliott, Takashi Hirata, Wenshan Lv, Fan Fan, Ying Ge, and George W. Booz
- Subjects
Vasculitis ,Epoxide hydrolase 2 ,Vascular smooth muscle ,Platelet Aggregation ,Endothelium ,Angiogenesis ,Neovascularization, Physiologic ,Pharmacology ,Article ,Muscle, Smooth, Vascular ,chemistry.chemical_compound ,Brain Injuries, Traumatic ,Hydroxyeicosatetraenoic Acids ,medicine ,Animals ,Humans ,Endothelial dysfunction ,Kidney ,Subarachnoid Hemorrhage ,medicine.disease ,20-Hydroxyeicosatetraenoic acid ,Stroke ,medicine.anatomical_structure ,chemistry ,Reperfusion Injury ,cardiovascular system ,Blood Vessels ,lipids (amino acids, peptides, and proteins) ,Arachidonic acid ,Endothelium, Vascular ,Signal Transduction ,circulatory and respiratory physiology - 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.
- Published
- 2016