Cytochrome P450 eicosanoids and cerebral vascular function. Expert Rev Mol Med 2011 Mar 01;13:e7
Date
03/02/2011Pubmed ID
21356152Pubmed Central ID
PMC3613250DOI
10.1017/S1462399411001773Scopus ID
2-s2.0-79956129813 (requires institutional sign-in at Scopus site) 61 CitationsAbstract
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.
Author List
Imig JD, Simpkins AN, Renic M, Harder DRMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidCerebrovascular Circulation
Cytochrome P-450 Enzyme System
Eicosanoids
Humans
Hydroxyeicosatetraenoic Acids