Abstract
The cytochrome (CYP) P450 epoxygenase pathway catalyzes the epoxidation of arachidonic acids to epoxyeicosatrienoic acids, which are subsequently hydrolyzed to less active dihydroxyeicosatrienoic acids by soluble epoxide hydrolase. Numerous preclinical studies have demonstrated that CYP-derived epoxyeicosatrienoic acids possess potent vasodilatory and anti-inflammatory properties in the cardiovascular system. In humans, functionally relevant polymorphisms, which may significantly modulate epoxyeicosatrienoic acid levels in vivo, have been identified in the genes encoding CYP2J2, CYP2C8, CYP2C9 and soluble epoxide hydrolase. Initial epidemiologic studies have demonstrated that genetic variation in the CYP epoxygenase pathway significantly modifies cardiovascular disease risk at the population level in humans, providing support for the hypothesis that modulation of this pathway may represent a novel approach to the prevention and treatment of cardiovascular disease. Future studies in humans validating these relationships and characterizing the underlying mechanisms will be necessary to fully understand the functional role of the CYP epoxygenase pathway in cardiovascular disease.
Acknowledgements
This work was supported by the Schering-Plough Rho Chi AFPE First-Year Graduate Student Scholarship, a Graduate School Merit Assistantship from the University of North Carolina at Chapel Hill (KNT), and an award from the American Heart Association (CRL)
Financial disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.