Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor.

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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Volpert OV,Zaichuk T,Zhou W,Reiher F,Ferguson TA,Stuart PM,Amin M,Bouck NP

doi

10.1038/nm0402-349

keywords:

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

349-57

issue

4

eissn

1078-8956

issn

1546-170X

pii

nm0402-349

journal_volume

8

pub_type

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