Inhibition of angiogenesis by Aβ peptides

Daniel Paris, Kirk Townsend, Amita Quadros, James Humphrey, Jiazhi Sun, Steven Brem, Marguerite Wotoczek-Obadia, Anthony DelleDonne, Nikunj Patel, Demian F. Obregon, Robert Crescentini, Laila Abdullah, Domenico Coppola, Amyn Mohammed Rojiani, Fiona Crawford, Saïd M. Sebti, Michael Mullan

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Aβ 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 Aβ on angiogenesis. We show that in vitro, Aβ dose-dependently inhibits the formation of capillaries by human brain endothelial cells plated on Matrigel and stimulates capillary degeneration at high doses. Preparations of Aβ peptides containing a higher content of β-sheet structures are more potently anti-angiogenic in vitro. Ex vivo, Aβ dose-dependently opposes angiogenesis in rat aortae and in human middle cerebral arteries. In vivo, Aβ 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 Aβ on human glioblastoma (U87MG) and human lung adenocarcinoma (A549) tumors. We show that intra-tumoral injection of Aβ 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, Aβ delivered intraperitoneally also suppressed the growth of human lung adenocarcinoma tumor xenografts. Altogether our data show that Aβ is an angiogenesis inhibitor.

Original languageEnglish (US)
Pages (from-to)75-85
Number of pages11
JournalAngiogenesis
Volume7
Issue number1
DOIs
StatePublished - Sep 6 2004
Externally publishedYes

Keywords

  • adenocarcinoma
  • angiogenesis
  • glioblastoma
  • β-amyloid

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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