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Cytochrome P450-Derived Lipid Mediators and Vascular Responses

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Endothelial Signaling in Development and Disease

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Abstract

Cytochrome P450 epoxygenases metabolize a spectrum of ω-6 and ω-3 polyunsaturated fatty acids such as arachidonic acid, linoleic acid, eicosapentaenoic acid, and docosahexenoic acid to generate bioactive lipid epoxide mediators. The epoxides thus generated demonstrate potent antihypertensive, angiogenic and anti-inflammatory properties. Endogenous epoxide levels are largely regulated by the soluble epoxide hydrolase (sEH), and the inhibition or genetic deletion of this enzyme increases epoxide concentrations and potentiates their biological actions. This review summarizes the mechanisms regulating epoxygenase and sEH, as well as the signaling event known to be regulated by the fatty acid epoxides and diols that can account for their vascular actions.

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Abbreviations

[Ca2+]i :

Intracellular Ca2+ concentration

BKCa :

Large conductance Ca2+-activated K+ channels

COX:

Cyclooxygenase

CREB:

cAMP-response element-binding protein

CYP:

Cytochrome P450

DHA:

Docosahexenoic acid

DHET:

Dihydroxyeicosatrienoic acid

EDHFs:

Endothelium-derived hyperpolarizing factors

EET:

Epoxyeicosatrienoic acid

EGF:

Epidermal growth factor

EPA:

Eicosapentaenoic acid

FABPs:

Fatty acid-binding proteins

HETE:

Hydroxyeicosatetraenoic acid

KCa :

Ca2+-dependent K+ channels

MKP-1:

MAP kinase phosphatase-1

MMP:

Matrix metalloproteinase

NFκB:

Nuclear factor κB

NO:

Nitric oxide

PI3-K:

Phosphatidylinositol 3-kinase

PKA:

Protein kinase A

PPAR:

Peroxisome proliferator-activated receptor

PUFA:

Polyunsaturated fatty acid

sEH:

Soluble epoxide hydrolase;

TRP channels:

Transient receptor potential channels

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Acknowledgments

The author acknowledges the work of the many groups whose work it has not been possible to cite here because of space limitations. Work performed in the author’s own laboratory was supported by the Deutsche Forschungsgemeinschaft (SFB-TR 23, A6 and Exzellenzcluster 147 ‘Cardio-Pulmonary System’).

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  1. Goethe University, Institute for Vascular Signalling, Theodor-Stern-Kai 7, 60590, Frankfurt/am Main, Germany

    Prof. Dr. Ingrid Fleming PhD

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    Mirko HH Schmidt

  2. Institute of Neurology Building 89, 4.Floor, R402, Goethe University Frankfurt School of Medicine, Frankfurt, Germany

    Stefan Liebner

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Fleming, I. (2015). Cytochrome P450-Derived Lipid Mediators and Vascular Responses. In: Schmidt, M., Liebner, S. (eds) Endothelial Signaling in Development and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2907-8_9

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