The cytochrome P450 pathway in angiogenesis and endothelial cell biology.
Long thought to be biologically important only as xenobiotic metabolizing enzymes, it is now clear that extrahepatic cytochrome P450 epoxygenases can utilize endogenous substrates such as arachidonic acid, linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid to generate bioactive lipid mediators. The epoxides thus generated can acutely affect vascular tone, and stimulate a spectrum of signaling pathways that affect growth-promoting kinase and transcription factor activity in vascular as well as cancer cells. Endogenous epoxide levels are largely controlled by the activity of the soluble epoxide hydrolase, and specific inhibitors of the enzyme as well as knockout mice are helping to determine the roles of these lipids in physiological and pathological angiogenesis. This review summarizes current knowledge on the aspects of the cytochrome P450/soluble epoxide hydrolase pathway related to vascular homeostasis and cancer.
Institute for Vascular Signalling, Centre for Molecular Medicine, Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. fleming@em.uni-frankfurt.de
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Fleming
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015777:Eicosanoids / Q000096:biosynthesis / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology* / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000201:enzymology; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000378:metabolism
D015777:Eicosanoids; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases