title: Cytochrome P450 eicosanoids and cerebral vascular function.
abstract: The eicosanoids 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs), which are generated from the metabolism of arachidonic acid by cytochrome P450 (CYP) enzymes, possess a wide array of biological actions, including the regulation of blood flow to organs. 20-HETE and EETs are generated in various cell types in the brain and cerebral blood vessels, and contribute significantly to cerebral blood flow autoregulation and the coupling of regional brain blood flow to neuronal activity (neurovascular coupling). Investigations are beginning to unravel the molecular and cellular mechanisms by which these CYP eicosanoids regulate cerebral vascular function and the changes that occur in pathological states. Intriguingly, 20-HETE and the soluble epoxide hydrolase (sEH) enzyme that regulates EET levels have been explored as molecular therapeutic targets for cerebral vascular diseases. Inhibition of 20-HETE, or increasing EET levels by inhibiting the sEH enzyme, decreases cerebral damage following stroke. The improved outcome following cerebral ischaemia is a consequence of improving cerebral vascular structure or function and protecting neurons from cell death. Thus, the CYP eicosanoids are key regulators of cerebral vascular function and novel therapeutic targets for cardiovascular diseases and neurological disorders.
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. jdimig@mcw.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Imig
authors.forename: Alexis N
authors.initials: AN
authors.lastname: Simpkins
authors.forename: Marija
authors.initials: M
authors.lastname: Renic
authors.forename: David R
authors.initials: DR
authors.lastname: Harder
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015777:Eicosanoids / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism
chemical_list: D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D015126:8,11,14-Eicosatrienoic Acid