The arachidonic acid epoxygenase is a component of the signaling mechanisms responsible for VEGF-stimulated angiogenesis.

Yang S, Wei S, Pozzi A, Capdevila JH
Arch Biochem Biophys. 2009 489 (1-2): 82-91

PMID: 19464254 · PMCID: PMC3786555 · DOI:10.1016/j.abb.2009.05.006

Cultured lung endothelial cells (LEC) respond to VEGF or arachidonic acid with increases in cell proliferation, the formation of tube-like structures, and the activation of Akt and ERK1/2 mediated growth pathways. LECs express a VEGF inducible Cyp2c44 epoxygenase and its 11,12- and 14,15-EET metabolites increase cell proliferation, tubulogenic activity, and the phosphorylation states of the ERK1/2 and Akt kinases. Ketoconazole, an epoxygenase inhibitor, blocks the cellular responses to VEGF. LECs expressing a Cyp2c44 epoxygenase small interference RNA show reductions in Cyp2c44 mRNA levels, and in their VEGF-stimulated proliferative and tubulogenic capacities; effects that are associated with decreases in VEGF-induced phosphorylation of the ERK1/2 and Akt kinases. We conclude that the Cyp2c44 arachidonic acid epoxygenase is a component of the signaling pathways associated with VEGF-stimulated angiogenesis, and suggest a role for EETs in the growth factor-induced changes in the activation states of the ERK1/2 and Akt kinase pathways.

MeSH Terms (21)

Animals Antifungal Agents Cell Proliferation Cells, Cultured Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Enzyme System Cytochrome P450 Family 2 Endothelial Cells Enzyme Activation Ketoconazole Lung MAP Kinase Signaling System Mice Mice, Transgenic Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Neovascularization, Physiologic Phosphorylation Proto-Oncogene Proteins c-akt RNA, Small Interfering Vascular Endothelial Growth Factor A

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