Tags

Type your tag names separated by a space and hit enter

Evaluation of cytochrome P450-derived eicosanoids in humans with stable atherosclerotic cardiovascular disease.
Atherosclerosis. 2012 Jun; 222(2):530-6.A

Abstract

OBJECTIVE

Preclinical and genetic epidemiologic studies suggest that modulating cytochrome P450 (CYP)-mediated arachidonic acid metabolism may have therapeutic utility in the management of coronary artery disease (CAD). However, predictors of inter-individual variation in CYP-derived eicosanoid metabolites in CAD patients have not been evaluated to date. Therefore, the primary objective was to identify clinical factors that influence CYP epoxygenase, soluble epoxide hydrolase (sEH), and CYP ω-hydroxylase metabolism in patients with established CAD.

METHODS

Plasma levels of epoxyeicosatrienoic acids (EETs), dihydroxyeicosatrienoic acids (DHETs), and 20-hydroxyeicosatetraenoic acid (20-HETE) were quantified by HPLC-MS/MS in a population of patients with stable, angiographically confirmed CAD (N=82) and healthy volunteers from the local community (N=36). Predictors of CYP epoxygenase, sEH, and CYP ω-hydroxylase metabolic function were evaluated by regression.

RESULTS

Obesity was significantly associated with low plasma EET levels and 14,15-EET:14,15-DHET ratios. Age, diabetes, and cigarette smoking also were significantly associated with CYP epoxygenase and sEH metabolic activity, while only renin-angiotensin system inhibitor use was associated with CYP ω-hydroxylase metabolic activity. Compared to healthy volunteers, both obese and non-obese CAD patients had significantly higher plasma EETs (P<0.01) and epoxide:diol ratios (P<0.01), whereas no difference in 20-HETE levels was observed (P=NS).

CONCLUSIONS

Collectively, these findings suggest that CYP-mediated eicosanoid metabolism is dysregulated in certain subsets of CAD patients, and demonstrate that biomarkers of CYP epoxygenase and sEH, but not CYP ω-hydroxylase, metabolism are altered in stable CAD patients relative to healthy individuals. Future studies are necessary to determine the therapeutic utility of modulating these pathways in patients with CAD.

Authors+Show Affiliations

Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22503544

Citation

Theken, Katherine N., et al. "Evaluation of Cytochrome P450-derived Eicosanoids in Humans With Stable Atherosclerotic Cardiovascular Disease." Atherosclerosis, vol. 222, no. 2, 2012, pp. 530-6.
Theken KN, Schuck RN, Edin ML, et al. Evaluation of cytochrome P450-derived eicosanoids in humans with stable atherosclerotic cardiovascular disease. Atherosclerosis. 2012;222(2):530-6.
Theken, K. N., Schuck, R. N., Edin, M. L., Tran, B., Ellis, K., Bass, A., Lih, F. B., Tomer, K. B., Poloyac, S. M., Wu, M. C., Hinderliter, A. L., Zeldin, D. C., Stouffer, G. A., & Lee, C. R. (2012). Evaluation of cytochrome P450-derived eicosanoids in humans with stable atherosclerotic cardiovascular disease. Atherosclerosis, 222(2), 530-6. https://doi.org/10.1016/j.atherosclerosis.2012.03.022
Theken KN, et al. Evaluation of Cytochrome P450-derived Eicosanoids in Humans With Stable Atherosclerotic Cardiovascular Disease. Atherosclerosis. 2012;222(2):530-6. PubMed PMID: 22503544.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of cytochrome P450-derived eicosanoids in humans with stable atherosclerotic cardiovascular disease. AU - Theken,Katherine N, AU - Schuck,Robert N, AU - Edin,Matthew L, AU - Tran,Bryant, AU - Ellis,Kyle, AU - Bass,Almasa, AU - Lih,Fred B, AU - Tomer,Kenneth B, AU - Poloyac,Samuel M, AU - Wu,Michael C, AU - Hinderliter,Alan L, AU - Zeldin,Darryl C, AU - Stouffer,George A, AU - Lee,Craig R, Y1 - 2012/03/27/ PY - 2011/11/29/received PY - 2012/02/24/revised PY - 2012/03/18/accepted PY - 2012/4/17/entrez PY - 2012/4/17/pubmed PY - 2012/9/21/medline SP - 530 EP - 6 JF - Atherosclerosis JO - Atherosclerosis VL - 222 IS - 2 N2 - OBJECTIVE: Preclinical and genetic epidemiologic studies suggest that modulating cytochrome P450 (CYP)-mediated arachidonic acid metabolism may have therapeutic utility in the management of coronary artery disease (CAD). However, predictors of inter-individual variation in CYP-derived eicosanoid metabolites in CAD patients have not been evaluated to date. Therefore, the primary objective was to identify clinical factors that influence CYP epoxygenase, soluble epoxide hydrolase (sEH), and CYP ω-hydroxylase metabolism in patients with established CAD. METHODS: Plasma levels of epoxyeicosatrienoic acids (EETs), dihydroxyeicosatrienoic acids (DHETs), and 20-hydroxyeicosatetraenoic acid (20-HETE) were quantified by HPLC-MS/MS in a population of patients with stable, angiographically confirmed CAD (N=82) and healthy volunteers from the local community (N=36). Predictors of CYP epoxygenase, sEH, and CYP ω-hydroxylase metabolic function were evaluated by regression. RESULTS: Obesity was significantly associated with low plasma EET levels and 14,15-EET:14,15-DHET ratios. Age, diabetes, and cigarette smoking also were significantly associated with CYP epoxygenase and sEH metabolic activity, while only renin-angiotensin system inhibitor use was associated with CYP ω-hydroxylase metabolic activity. Compared to healthy volunteers, both obese and non-obese CAD patients had significantly higher plasma EETs (P<0.01) and epoxide:diol ratios (P<0.01), whereas no difference in 20-HETE levels was observed (P=NS). CONCLUSIONS: Collectively, these findings suggest that CYP-mediated eicosanoid metabolism is dysregulated in certain subsets of CAD patients, and demonstrate that biomarkers of CYP epoxygenase and sEH, but not CYP ω-hydroxylase, metabolism are altered in stable CAD patients relative to healthy individuals. Future studies are necessary to determine the therapeutic utility of modulating these pathways in patients with CAD. SN - 1879-1484 UR - https://www.unboundmedicine.com/medline/citation/22503544/Evaluation_of_cytochrome_P450_derived_eicosanoids_in_humans_with_stable_atherosclerotic_cardiovascular_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(12)00208-0 DB - PRIME DP - Unbound Medicine ER -