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Pharmaceutics 2017, 9(4), 44; https://doi.org/10.3390/pharmaceutics9040044

Altered Protein Expression of Cardiac CYP2J and Hepatic CYP2C, CYP4A, and CYP4F in a Mouse Model of Type II Diabetes—A Link in the Onset and Development of Cardiovascular Disease?

1
Faculté de Pharmacie, Université Laval, 1050 Avenue de la Médecine, Québec, QC G1V 0A6, Canada
2
Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Sainte-Foy, Québec, QC G1V 4G5, Canada
*
Author to whom correspondence should be addressed.
Received: 25 August 2017 / Revised: 30 September 2017 / Accepted: 6 October 2017 / Published: 12 October 2017
(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)
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Abstract

Arachidonic acid can be metabolized by cytochrome P450 (CYP450) enzymes in a tissue- and cell-specific manner to generate vasoactive products such as epoxyeicosatrienoic acids (EETs-cardioprotective) and hydroxyeicosatetraenoic acids (HETEs-cardiotoxic). Type II diabetes is a well-recognized risk factor for developing cardiovascular disease. A mouse model of Type II diabetes (C57BLKS/J-db/db) was used. After sacrifice, livers and hearts were collected, washed, and snap frozen. Total proteins were extracted. Western blots were performed to assess cardiac CYP2J and hepatic CYP2C, CYP4A, and CYP4F protein expression, respectively. Significant decreases in relative protein expression of cardiac CYP2J and hepatic CYP2C were observed in Type II diabetes animals compared to controls (CYP2J: 0.80 ± 0.03 vs. 1.05 ± 0.06, n = 20, p < 0.001); (CYP2C: 1.56 ± 0.17 vs. 2.21 ± 0.19, n = 19, p < 0.01). In contrast, significant increases in relative protein expression of both hepatic CYP4A and CYP4F were noted in Type II diabetes mice compared to controls (CYP4A: 1.06 ± 0.09 vs. 0.18 ± 0.01, n = 19, p < 0.001); (CYP4F: 2.53 ± 0.22 vs. 1.10 ± 0.07, n = 19, p < 0.001). These alterations induced by Type II diabetes in the endogenous pathway (CYP450) of arachidonic acid metabolism may increase the risk for cardiovascular disease by disrupting the fine equilibrium between cardioprotective (CYP2J/CYP2C-generated) and cardiotoxic (CYP4A/CYP4F-generated) metabolites of arachidonic acid. View Full-Text
Keywords: arachidonic acid; CYP450 enzymes; Type II diabetes; cardiovascular disease arachidonic acid; CYP450 enzymes; Type II diabetes; cardiovascular disease
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Drolet, B.; Pilote, S.; Gélinas, C.; Kamaliza, A.-D.; Blais-Boilard, A.; Virgili, J.; Patoine, D.; Simard, C. Altered Protein Expression of Cardiac CYP2J and Hepatic CYP2C, CYP4A, and CYP4F in a Mouse Model of Type II Diabetes—A Link in the Onset and Development of Cardiovascular Disease? Pharmaceutics 2017, 9, 44.

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