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Cytochrome P450-derived eicosanoids and heart function.
Pharmacol Ther. 2017 Nov; 179:47-83.P&T

Abstract

The cytochrome P450 monooxygenase system (CYP) is a multigene superfamily of enzymes, which are important in the metabolism of foreign and endogenous compounds. CYP isoforms metabolize a number of n-3 and n-6 polyunsaturated fatty acids (PUFA), including linoleic acid (18:2n6, LA), arachidonic acid (20:4n6, AA), ecosapentaenoic acid (20:5n3, EPA) and docosahexaenoic acid (22:6n3, DHA) into bioactive lipid mediators, termed eicosanoids. CYP-derived eicosanoids have numerous effects toward physiological and pathophysiological events within the body, which depends on the type, quantity and timing of metabolites produced. Alterations in fatty acid composition and concentrations have been shown to have a role in cardiovascular disease (CVD). The functional role of CYP isozymes and CYP-derived eicosanoids toward physiological and pathophysiological processes in the heart is a rapidly expanding field of research. Numerous studies have investigated the beneficial and detrimental effects of CYP epoxygenase derived metabolites of AA, epoxyeicosatrienoic acids (EET) and CYP ω-hydroxylase products, hydroxyeicosatetraenoic acids (HETE), toward both cardiac and vascular function and disease. Emerging research is revealing the importance of other lipid mediators generated from CYP isozymes, such as epoxyeicosatetraenoic acids (EEQ) and epoxydocosapentaenoic acids (EDP), formed from the metabolism of EPA and DHA and metabolites of LA. Important determinants such as genetics, gender and age have a role in regulating the CYP-derived eicosanoids produced from the metabolism n-3 and n-6 PUFA. Obtaining a better understanding of the complex role CYP-derived eicosanoids have within the heart will provide valuable insight for both basic and clinical researchers investigation CVD.

Authors+Show Affiliations

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada; Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Canada. Electronic address: jseubert@ualberta.ca.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28551025

Citation

Jamieson, K Lockhart, et al. "Cytochrome P450-derived Eicosanoids and Heart Function." Pharmacology & Therapeutics, vol. 179, 2017, pp. 47-83.
Jamieson KL, Endo T, Darwesh AM, et al. Cytochrome P450-derived eicosanoids and heart function. Pharmacol Ther. 2017;179:47-83.
Jamieson, K. L., Endo, T., Darwesh, A. M., Samokhvalov, V., & Seubert, J. M. (2017). Cytochrome P450-derived eicosanoids and heart function. Pharmacology & Therapeutics, 179, 47-83. https://doi.org/10.1016/j.pharmthera.2017.05.005
Jamieson KL, et al. Cytochrome P450-derived Eicosanoids and Heart Function. Pharmacol Ther. 2017;179:47-83. PubMed PMID: 28551025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytochrome P450-derived eicosanoids and heart function. AU - Jamieson,K Lockhart, AU - Endo,Tomoko, AU - Darwesh,Ahmed M, AU - Samokhvalov,Victor, AU - Seubert,John M, Y1 - 2017/05/25/ PY - 2017/5/30/pubmed PY - 2018/6/8/medline PY - 2017/5/29/entrez KW - CYP enzymes KW - Eicosanoids KW - Heart KW - N-3 polyunsaturated fatty acids KW - N-6 polyunsaturated fatty acids SP - 47 EP - 83 JF - Pharmacology & therapeutics JO - Pharmacol Ther VL - 179 N2 - The cytochrome P450 monooxygenase system (CYP) is a multigene superfamily of enzymes, which are important in the metabolism of foreign and endogenous compounds. CYP isoforms metabolize a number of n-3 and n-6 polyunsaturated fatty acids (PUFA), including linoleic acid (18:2n6, LA), arachidonic acid (20:4n6, AA), ecosapentaenoic acid (20:5n3, EPA) and docosahexaenoic acid (22:6n3, DHA) into bioactive lipid mediators, termed eicosanoids. CYP-derived eicosanoids have numerous effects toward physiological and pathophysiological events within the body, which depends on the type, quantity and timing of metabolites produced. Alterations in fatty acid composition and concentrations have been shown to have a role in cardiovascular disease (CVD). The functional role of CYP isozymes and CYP-derived eicosanoids toward physiological and pathophysiological processes in the heart is a rapidly expanding field of research. Numerous studies have investigated the beneficial and detrimental effects of CYP epoxygenase derived metabolites of AA, epoxyeicosatrienoic acids (EET) and CYP ω-hydroxylase products, hydroxyeicosatetraenoic acids (HETE), toward both cardiac and vascular function and disease. Emerging research is revealing the importance of other lipid mediators generated from CYP isozymes, such as epoxyeicosatetraenoic acids (EEQ) and epoxydocosapentaenoic acids (EDP), formed from the metabolism of EPA and DHA and metabolites of LA. Important determinants such as genetics, gender and age have a role in regulating the CYP-derived eicosanoids produced from the metabolism n-3 and n-6 PUFA. Obtaining a better understanding of the complex role CYP-derived eicosanoids have within the heart will provide valuable insight for both basic and clinical researchers investigation CVD. SN - 1879-016X UR - https://www.unboundmedicine.com/medline/citation/28551025/Cytochrome_P450_derived_eicosanoids_and_heart_function_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0163-7258(17)30124-9 DB - PRIME DP - Unbound Medicine ER -