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Detection of human CYP2Cs in heart, aorta and coronary tissues
Author(s) -
DeLozier Tracy C.,
Dai Diana,
Coulter Sherry J.,
Bradbury J. Alyce,
Murphy Elizabeth,
Zeldin Darryl C.,
Goldstein Joyce A.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1111-c
Subject(s) - cyp2c9 , aorta , medicine , myocardial infarction , coronary arteries , endogeny , cyp2c8 , endocrinology , cardiology , biology , artery , pharmacology , cytochrome p450 , metabolism
CYP2C and CYP2J enzymes metabolize arachidonic to epoxyeicosatrienoic acids (EETs). Expression of these enzymes in the cardiovascular system may have a direct relationship to hypertension and cardiovascular diseases, such as acute myocardial infarction (AMI). CYP2C polymorphisms have also been reported to result in an increased risk of AMI. Drugs that inhibit CYP2C9 activity are cardioprotective in animal models of reperfusion injury. In this study, normal heart, coronary and aorta tissues were obtained from individuals of various ages, sex and races. We then measured the abundance of CYP2C8, CYP2C9 and CYP2J2, in human heart, aorta and coronary samples by Real‐time PCR, immunoblotting and immunohistochemistry. Immunoblotting results show that CYP2J2 and CYP2C8 were detected in human heart, coronary vessels and aorta. The relative abundance of CYP2C9 and CYP2J2 mRNA were highly variable in human heart from different individuals, CYP2C8 was detected in only 1/8 hearts. In contrast, in human aorta, CYP2C9 mRNA levels were ~100‐fold higher than either CYP2J2 or CYP2C8. In coronary artery, the levels of CYP2C9, CYP2J2, and CYP2C8 mRNA were more comparable but in general CYP2C9 was slightly higher. The presence of CYP2C9, and CYP2J2 and somewhat lower levels of CYP2C8 in cardiovascular tissues suggests that CYP2C9 and CYP2J2 have physiologically relevant roles in the production of vasoactive eicosanoids which may be important in modulating vascular tone and homeostasis. This research was supported by the intramural division of the NIEHS.