Article

Cytochrome P450 epoxygenases, soluble epoxide hydrolase, and the regulation of cardiovascular inflammation.

Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599-7569, USA.
Journal of Molecular and Cellular Cardiology (impact factor: 5.17). 11/2009; 48(2):331-41. DOI:10.1016/j.yjmcc.2009.10.022 pp.331-41
Source: PubMed

ABSTRACT The cytochrome P450 (CYP) epoxygenase enzymes CYP2J and CYP2C catalyze the epoxidation of arachidonic acid to epoxyeicosatrienoic acids (EETs), which are rapidly hydrolyzed to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). It is well-established that CYP epoxygenase-derived EETs possess potent vasodilatory effects; however, the cellular effects of EETs and their regulation of various inflammatory processes have become increasingly appreciated in recent years, suggesting that the role of this pathway in the cardiovascular system extends beyond the maintenance of vascular tone. In particular, CYP epoxygenase-derived EETs inhibit endothelial activation and leukocyte adhesion via attenuation of nuclear factor-kappaB activation, inhibit hemostasis, protect against myocardial ischemia-reperfusion injury, and promote endothelial cell survival via modulation of multiple cell signaling pathways. Thus, the CYP epoxygenase pathway is an emerging target for pharmacological manipulation to enhance the cardiovascular protective effects of EETs. This review will focus on the role of the CYP epoxygenase pathway in the regulation of cardiovascular inflammation and (1) describe the functional impact of CYP epoxygenase-derived EET biosynthesis and sEH-mediated EET hydrolysis on key inflammatory process in the cardiovascular system, (2) discuss the potential relevance of this pathway to pathogenesis and treatment of cardiovascular disease, and (3) identify areas for future research.

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Keywords

arachidonic acid
 
cardiovascular protective effects
 
CYP epoxygenase-derived EET biosynthesis
 
CYP2C catalyze
 
dihydroxyeicosatrienoic acids
 
emerging target
 
endothelial activation
 
endothelial cell survival
 
epoxyeicosatrienoic acids
 
future research
 
key inflammatory process
 
leukocyte adhesion
 
multiple cell signaling pathways
 
myocardial ischemia-reperfusion injury
 
nuclear factor-kappaB activation
 
potent vasodilatory effects
 
recent years
 
sEH-mediated EET hydrolysis
 
soluble epoxide hydrolase
 
various inflammatory processes
 

Yangmei Deng