Inhibition of Angiogenesis by Aβ Peptides

A β peptides are naturally occurring peptides forming β -sheet aggregates that constitute an integral component of senile plaques and vascular deposits in Alzheimer's disease. Since several peptides adopting a β -sheet conformation have been shown to be anti-angiogenic, we investigated the effect of A β on angiogenesis. We show that in vitro , A β dose-dependently inhibits the formation of capillaries by human brain endothelial cells plated on Matrigel and stimulates capillary degeneration at high doses. Preparations of A β peptides containing a higher content of β -sheet structures are more potently anti-angiogenic in vitro . Ex vivo , A β dose-dependently opposes angiogenesis in rat aortae and in human middle cerebral arteries. In vivo , A β 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 A β on human glioblastoma (U87MG) and human lung adenocarcinoma (A549) tumors. We show that intra-tumoral injection of A β 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, A β delivered intraperitoneally also suppressed the growth of human lung adenocarcinoma tumor xenografts. Altogether our data show that A β is an angiogenesis inhibitor.