Angiogenesis. 2004;7(1):75-85.
Inhibition
of angiogenesis by Abeta peptides.
Paris D, Townsend K, Quadros
A, Humphrey J, Sun J, Brem
S, Wotoczek-Obadia
M, DelleDonne
A, Patel N, Obregon
DF, Crescentini
R, Abdullah L, Coppola D, Rojiani
AM, Crawford F, Sebti
SM, Mullan
M.
The Roskamp Institute,
Abeta peptides are naturally occurring peptides
forming beta-sheet aggregates that constitute an integral component of senile
plaques and vascular deposits in Alzheimer's disease. Since several peptides
adopting a beta-sheet conformation have been shown to be anti-angiogenic, we investigated the effect of Abeta on angiogenesis. We show that in vitro,
Abeta dose-dependently inhibits the formation of
capillaries by human brain endothelial cells plated on Matrigel
and stimulates capillary degeneration at high doses. Preparations of Abeta peptides containing a higher content of beta-sheet
structures are more potently anti-angiogenic in
vitro. Ex vivo, Abeta dose-dependently opposes
angiogenesis in rat aortae and in human middle cerebral
arteries. In vivo, Abeta dose dependently inhibits
angiogenesis in the chick chorioallantoic membrane
assay and suppresses bFGF-induced blood vessel
formation in the corneal micropocket and Matrigel plug assays. Since angiogenesis is required for
tumor growth, we explored the effect of Abeta on
human glioblastoma (U87MG) and human lung adenocarcinoma (A549) tumors. We show that intra-tumoral injection of Abeta
potently inhibits the growth and vascularization of
human glioblastoma and human lung adenocarcinoma
tumor xenografts in nude mice. Similarly to the
intra-tumoral injection regimen, Abeta
delivered intraperitoneally also suppressed the
growth of human lung adenocarcinoma tumor xenografts. Altogether our data show that Abeta is an angiogenesis inhibitor.
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Keywords: Angiogenesis, Abeta, peptides