Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium–derived factor View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-04

AUTHORS

Olga V. Volpert, Tetiana Zaichuk, Wei Zhou, Frank Reiher, Thomas A. Ferguson, P. Michael Stuart, Mohammad Amin, Noel P. Bouck

ABSTRACT

Natural inhibitors of angiogenesis are able to block pathological neovascularization without harming the preexisting vasculature. Here we show that two such inhibitors, thrombospondin-1 and pigment epithelium-derived factor, derive specificity for remodeling vessels from their dependence on Fas/Fas ligand (FasL)-mediated apoptosis to block angiogenesis. Both inhibitors upregulated FasL on endothelial cells. Expression of the essential partner of FasL, Fas/CD95 receptor, was low on quiescent endothelial cells and vessels but greatly enhanced by inducers of angiogenesis, thereby specifically sensitizing the stimulated cells to apoptosis by inhibitor-generated FasL. The anti-angiogenic activity of thrombospondin-1 and pigment epithelium-derived factor both in vitro and in vivo was dependent on this dual induction of Fas and FasL and the resulting apoptosis. This example of cooperation between pro- and anti-angiogenic factors in the inhibition of angiogenesis provides one explanation for the ability of inhibitors to select remodeling capillaries for destruction. More... »

PAGES

349

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm0402-349

DOI

http://dx.doi.org/10.1038/nm0402-349

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004091227

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11927940


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