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Cytochrome P450 Enzymes in the Bioactivation of Polyunsaturated Fatty Acids and Their Role in Cardiovascular Disease

  • Christina Westphal
  • Anne Konkel
  • Wolf-Hagen SchunckEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 851)

Abstract

Various members of the cytochrome P450 (CYP) superfamily have the capacity of metabolizing omega-6 and omega-3 polyunsaturated fatty acids (n-6 and n-3 PUFAs). In most mammalian tissues, CYP2C and CYP2J enzymes are the major PUFA epoxygenases, whereas CYP4A and CYP4F subfamily members function as PUFA hydroxylases. The individual CYP enzymes differ in their substrate specificities as well as regio- and stereoselectivities and thus produce distinct sets of epoxy and/or hydroxy metabolites, collectively termed CYP eicosanoids. Nutrition has a major impact on the endogenous CYP-eicosanoid profile. “Western diets” rich in n-6 PUFAs result in a predominance of arachidonic acid-derived metabolites, whereas marine foodstuffs rich in n-3 PUFAs shift the profile to eicosapentaenoic and docosahexaenoic acid-derived metabolites. In general, CYP eicosanoids are formed as second messengers of numerous hormones, growth factors and cytokines regulating cardiovascular and renal function, and a variety of other physiological processes. Imbalances in the formation of individual CYP eicosanoids are linked to the development of hypertension, myocardial infarction, maladaptive cardiac hypertrophy, acute kidney injury, stroke and inflammatory disorders. The underlying mechanisms are increasingly understood and may provide novel targets for the prevention and treatment of these disease states. Suitable pharmacological agents are under development and first proofs of concept have been obtained in animal models.

Keywords

Arachidonic acid Eicosapentaenoic acid Docosahexaenoic acid Hydroxylases Epoxygenases Hypertension Ischemia/reperfusion injury Cardiac hypertrophy 

Notes

Acknowledgments

This review is dedicated to the late John Charles (Jack) McGiff, MD and Professor of Pharmacology. Professor McGiff made seminal discoveries on the role of CYP eicosanoids in blood pressure regulation and he inspired many students and colleagues to follow his way of successfully combining biochemistry and pathophysiology for understanding the mechanisms of complex cardiovascular diseases. This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG): Schu822/5; FOR 1054 and Schu822/7-1; FOR 1368.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Christina Westphal
    • 1
  • Anne Konkel
    • 1
  • Wolf-Hagen Schunck
    • 1
    Email author
  1. 1.Max Delbrueck Center for Molecular MedicineBerlinGermany

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