Research ArticleAngiogenesis

The interaction of heparan sulfate proteoglycans with endothelial transglutaminase-2 limits VEGF165-induced angiogenesis

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Science Signaling  14 Jul 2015:
Vol. 8, Issue 385, pp. ra70
DOI: 10.1126/scisignal.aaa0963

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Preventing angiogenesis

Limiting angiogenesis, the process of blood vessel formation, is desirable in various clinical contexts. Proteins of the VEGF family are key angiogenic factors, and some VEGF isoforms bind to heparan sulfate proteoglycans along with the receptor VEGFR2 to stimulate angiogenesis. Beckouche et al. found that transglutaminase-2, a cross-linking enzyme that can be released by endothelial cells, prevented a specific VEGF isoform from binding to heparan sulfate proteoglycans. Mice lacking transglutaminase-2 had increased retinal angiogenesis. In addition, the sprouting of endothelial capillaries in response to this VEGF isoform was increased when the cells were deficient in transglutaminase-2.

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