Nie D, Tang K, Diglio C, Honn KVEicosanoid regulation of angiogenesis: role of endothelial arachidonate 12-lipoxygenase. Blood 95(7): 2304-2311

Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, MI, USA.
Blood (Impact Factor: 10.45). 05/2000; 95(7):2304-11.
Source: PubMed


Angiogenesis, the formation of new capillaries from preexisting blood vessels, is a multistep, highly orchestrated process involving vessel sprouting, endothelial cell migration, proliferation, tube differentiation, and survival. Eicosanoids, arachidonic acid (AA)-derived metabolites, have potent biologic activities on vascular endothelial cells. Endothelial cells can synthesize various eicosanoids, including the 12-lipoxygenase (LOX) product 12(S)-hydroxyeicosatetraenoic acid (HETE). Here we demonstrate that endogenous 12-LOX is involved in endothelial cell angiogenic responses. First, the 12-LOX inhibitor, N-benzyl-N-hydroxy-5-phenylpentanamide (BHPP), reduced endothelial cell proliferation stimulated either by basic fibroblast growth factor (bFGF) or by vascular endothelial growth factor (VEGF). Second, 12-LOX inhibitors blocked VEGF-induced endothelial cell migration, and this blockage could be partially reversed by the addition of 12(S)-HETE. Third, pretreatment of an angiogenic endothelial cell line, RV-ECT, with BHPP significantly inhibited the formation of tubelike/cordlike structures within Matrigel. Fourth, overexpression of 12-LOX in the CD4 endothelial cell line significantly stimulated cell migration and tube differentiation. In agreement with the critical role of 12-LOX in endothelial cell angiogenic responses in vitro, the 12-LOX inhibitor BHPP significantly reduced bFGF-induced angiogenesis in vivo using a Matrigel implantation bioassay. These findings demonstrate that AA metabolism in endothelial cells, especially the 12-LOX pathway, plays a critical role in angiogenesis.

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Available from: Clement A Diglio, Mar 24, 2014
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    • "Also the tube formation of human microvessel endothelial cells, which was inhibited by a galloyl glucose derivate, was most likely due to the inhibition of cell migration (Lee et al, 2004). Because 12/15-LOX contributes to angiogenesis (Nie et al, 2000, 2006; Rose and Connolly, 2000) and tumour metastasis (Liu et al, 1996; Jankun et al, 2006), di-GA may prevent neo-vascularisation of tumours as well as infiltration of cancer cells into the lymphatic vasculature. Another derivate, galloyl glucose, blocked HT-1080 tumour invasion through gelatin by inhibiting matrix metalloprotease-2 (MMP-2) and MMP-9 (Ata et al, 1996). "
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