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E. Van Aken, L. Morbidelli, L. De Rijcke, M. Ziche, M. Mareel, J. De Laey; Plasmin Produces Proangiogenic Fragments . Invest. Ophthalmol. Vis. Sci. 2003;44(13):556.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Angiogenesis produces new vessels from endothelial cells that invade from pre-existing vessels. Endothelial cells express two types of Ca2+ dependent cell-cell adhesion molecules: V(ascular)E(ndothelial)-cadherin, specific for endothelial cells, and N(eural)-cadherin, present also in retinal cells, fibroblasts, myocytes, pericytes. Ectodomain shedding releases soluble fragments (sN-CAD) from the extra-cellular domain of N-cadherin. We investigated whether sN-CAD would stimulate the invasion of endothelial cells and so exert a pro-angiogenic activity. Methods: ARM cells are mouse sarcoma cells transfected with cDNA encoding chicken N-cadherin; when treated with plasmin their conditioned medium is a soure of sN-CAD, that can be removed by immunodepletion. The rabbit cornea assay and chorio-allantoic membrane assay are used as in vivo angiogenesis assays. Results: ARM-conditioned medium stimulates angiogenesis in the chick chorio-allantoic membrane and the rabbit cornea, and this pro-angiogenic activity is abolished by immunodepletion of the conditioned medium. 10-mer HAV-comprising peptide, identical to aminoacid 235 to 244 from human N-cadherin, revealed the HAV sequence as crucial for the pro-angiogenic effect of sN-CAD. In the rabbit cornea, high doses (10µg and 50µg) of the HAV-comprising peptide, stimulated angiogensis, and a low dose (200ng) potentiated FGF-2 stimulated angiogenesis. Conclusions: Our results suggest that ectodomaine shedding of N-cadherin stimulates angiogenesis.
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