Cytochrome P450 2C8 (CYP2C8)

CYP2C8 is one of the major drug-metabolizing CYP450 isoforms. The induction of CYP2C8 in native porcine coronary artery endothelial cells by beta-naphthoflavone enhances the formation of 11,12-epoxyeicosatrienoic acid, as well as endothelium-derived hyperpolarizing factor-mediated hyperpolarization and relaxation. Transfection of coronary arteries with CYP2C8 antisense oligonucleotides resulted in decreased levels of CYP2C and attenuated the endothelium-derived hyperpolarizing factor-mediated vascular responses. Thus, a CYP-epoxygenase product is an essential component of the endothelium-derived hyperpolarizing factor-mediated relaxation in the porcine coronary artery, and CYP2C8 fulfills the criteria for the coronary endothelium-derived hyperpolarization factor synthase.