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Received for publication September 13, 2006.
Revised December 29, 2006.
Accepted for publication January 5, 2007.
The cytochrome P450 (CYP) enzymes CYP2C8, CYP2C9, and CYP2J2 metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), which are known to be vital in regulation of vascular tone and cardiovascular homeostasis. Since there is limited information regarding the relative expression of these CYP enzymes in cardiovascular tissues, this study examined the expression of CYP2C8, CYP2C9 and CYP2J2 mRNA and protein in human heart, aorta and coronary artery samples by real-time PCR, immunoblotting and immunohistochemistry. CYP2J2 and CYP2C9 mRNA levels were highly variable in human hearts, while CYP2C8 mRNA was present in lower abundance. CYP2J2 mRNA was approximately 1000 times higher than CYP2C9 or CYP2C8 in human heart. However, CYP2C9 mRNA was more abundant than CYP2J2 or CYP2C8 in one ischemic heart. In human aorta, mean CYP2C9 mRNA levels were ~ 50 times higher than CYP2J2 and 5-fold higher than CYP2C8. In human coronary artery, mean values for CYP2C9 mRNA were ~ 2-fold higher than CYP2J2 mRNA and 6-fold higher than CYP2C8 mRNA. Immunoblotting results show relatively high levels of CYP2J2 and CYP2C8 protein in human hearts, which was confirmed by immunohistochemistry. CYP2C9 protein was also detected at high levels in one ischemic heart by immunoblotting. CYP2C9 was present at higher levels than CYPJ2 in aorta and coronary artery, while CYP2C8 protein was below the limits of detection. The expression of CYP2J2 and CYP2C8 in human heart, and CYPC9 and CYP2J2 in aorta and coronary artery is consistent with a physiological role for these enzymes in these tissues.
Key words:
CYP2C, cytochrome P450, cytochrome P450 isoforms, extrahepatic cytochrome P450, extrahepatic drug metabolism, human CYP enzymes
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