Cytochrome P450 epoxygenases 2C8 and 2C9 are implicated in hypoxia-induced endothelial cell migration and angiogenesis - PubMed (original) (raw)
. 2005 Dec 1;118(Pt 23):5489-98.
doi: 10.1242/jcs.02674. Epub 2005 Nov 15.
Affiliations
- PMID: 16291720
- DOI: 10.1242/jcs.02674
Cytochrome P450 epoxygenases 2C8 and 2C9 are implicated in hypoxia-induced endothelial cell migration and angiogenesis
U Ruth Michaelis et al. J Cell Sci. 2005.
Abstract
Recent studies suggest that cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids (EETs) elicit cell proliferation and promote angiogenesis. The aim of this study was to determine the role of CYP 2C8/9-derived EETs in the process of angiogenesis under hypoxic conditions. In human endothelial cells, hypoxia enhanced the activity of the CYP 2C9 promoter, increased the expression of CYP 2C mRNA and protein and augmented 11,12-EET production. In Transwell assays, the migration of endothelial cells pre-exposed to hypoxia to increase CYP expression was abolished by CYP 2C antisense oligonucleotides as well as by the CYP inhibitor MS-PPOH and the EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE). Similar findings were obtained in porcine coronary artery endothelial cells. CYP 2C9 overexpression in endothelial cells increased the association of PAK-1 with Rac, a response also elicited by the CYP 2C9 product 11,12-EET. Matrix metalloprotease (MMP) activity was increased in CYP-2C9-overexpressing cells and correlated with increased invasion through Matrigel-coated Transwell chambers: an effect sensitive to the CYP 2C9 inhibitor sulfaphenazole as well as to EEZE and the MMP inhibitor GM6001. In in vitro angiogenesis models, the EET antagonist inhibited tube formation induced by CYP 2C9 overexpression as well as that in endothelial cells exposed to hypoxia to increase CYP 2C expression. Furthermore, in the chick chorioallantoic membrane assay, EEZE abolished hypoxia-induced angiogenesis. Taken together, these data indicate that CYP 2C-derived EETs significantly affect the sequence of angiogenic events under hypoxic conditions.
Similar articles
- Role of cytochrome P450 2C epoxygenases in hypoxia-induced cell migration and angiogenesis in retinal endothelial cells.
Michaelis UR, Xia N, Barbosa-Sicard E, Falck JR, Fleming I. Michaelis UR, et al. Invest Ophthalmol Vis Sci. 2008 Mar;49(3):1242-7. doi: 10.1167/iovs.07-1087. Invest Ophthalmol Vis Sci. 2008. PMID: 18326754 - Cytochrome P450 2C9-derived epoxyeicosatrienoic acids induce angiogenesis via cross-talk with the epidermal growth factor receptor (EGFR).
Michaelis UR, Fisslthaler B, Medhora M, Harder D, Fleming I, Busse R. Michaelis UR, et al. FASEB J. 2003 Apr;17(6):770-2. doi: 10.1096/fj.02-0640fje. Epub 2003 Feb 5. FASEB J. 2003. PMID: 12586744 - Cytochrome P4502C9-derived epoxyeicosatrienoic acids induce the expression of cyclooxygenase-2 in endothelial cells.
Michaelis UR, Falck JR, Schmidt R, Busse R, Fleming I. Michaelis UR, et al. Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):321-6. doi: 10.1161/01.ATV.0000151648.58516.eb. Epub 2004 Nov 29. Arterioscler Thromb Vasc Biol. 2005. PMID: 15569819 - Epoxyeicosatrienoic acids, cell signaling and angiogenesis.
Fleming I. Fleming I. Prostaglandins Other Lipid Mediat. 2007 Jan;82(1-4):60-7. doi: 10.1016/j.prostaglandins.2006.05.003. Epub 2006 Jul 11. Prostaglandins Other Lipid Mediat. 2007. PMID: 17164133 Review. - From endothelium-derived hyperpolarizing factor (EDHF) to angiogenesis: Epoxyeicosatrienoic acids (EETs) and cell signaling.
Michaelis UR, Fleming I. Michaelis UR, et al. Pharmacol Ther. 2006 Sep;111(3):584-95. doi: 10.1016/j.pharmthera.2005.11.003. Epub 2005 Dec 27. Pharmacol Ther. 2006. PMID: 16380164 Review.
Cited by
- Updates on osteonecrosis of the jaw.
Yamashita J, McCauley LK, Van Poznak C. Yamashita J, et al. Curr Opin Support Palliat Care. 2010 Sep;4(3):200-6. doi: 10.1097/SPC.0b013e32833d303b. Curr Opin Support Palliat Care. 2010. PMID: 20657284 Free PMC article. Review. - Sexually Dimorphic Regulation of EET Synthesis and Metabolism: Roles of Estrogen.
Huang A, Sun D. Huang A, et al. Front Pharmacol. 2018 Oct 29;9:1222. doi: 10.3389/fphar.2018.01222. eCollection 2018. Front Pharmacol. 2018. PMID: 30420806 Free PMC article. - Cytochrome P450 2C8 ω3-long-chain polyunsaturated fatty acid metabolites increase mouse retinal pathologic neovascularization--brief report.
Shao Z, Fu Z, Stahl A, Joyal JS, Hatton C, Juan A, Hurst C, Evans L, Cui Z, Pei D, Gong Y, Xu D, Tian K, Bogardus H, Edin ML, Lih F, Sapieha P, Chen J, Panigrahy D, Hellstrom A, Zeldin DC, Smith LE. Shao Z, et al. Arterioscler Thromb Vasc Biol. 2014 Mar;34(3):581-6. doi: 10.1161/ATVBAHA.113.302927. Epub 2014 Jan 23. Arterioscler Thromb Vasc Biol. 2014. PMID: 24458713 Free PMC article. - Inhibition of the soluble epoxide hydrolase attenuates monocrotaline-induced pulmonary hypertension in rats.
Revermann M, Barbosa-Sicard E, Dony E, Schermuly RT, Morisseau C, Geisslinger G, Fleming I, Hammock BD, Brandes RP. Revermann M, et al. J Hypertens. 2009 Feb;27(2):322-31. doi: 10.1097/hjh.0b013e32831aedfa. J Hypertens. 2009. PMID: 19226702 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
Miscellaneous