Cytochrome P450 eicosanoids and cerebral vascular function

John D. Imig; Alexis N. Simpkins; Marija Renic; David R. Harder

doi:10.1017/S1462399411001773

Cytochrome P450 eicosanoids and cerebral vascular function

Published online by Cambridge University Press: 01 March 2011

Marija Renic and

John D. Imig*: Affiliation:
Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA. Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Alexis N. Simpkins: Affiliation:
Medical College of Georgia, Augusta, GA, USA.
Marija Renic: Affiliation:
Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, USA.
David R. Harder: Affiliation:
Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, USA. Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
*: *Corresponding author: John D. Imig, Department of Pharmacology and Toxicology, Cardiovascular Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. E-mail: jdimig@mcw.edu

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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.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 13 , March 2011 , e7

DOI: https://doi.org/10.1017/S1462399411001773 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2011

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Cytochrome P450 eicosanoids and cerebral vascular function

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