Cited by 148Angiogenesis and VEGF in CancerAlzheimer's disease research and treatmentsBarrier Structure and Function Studies

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Inhibition of Angiogenesis by Aβ Peptides

Paris, Daniel, Townsend, Kirk, Quadros, Amita, Humphrey, James, Sun, Jiazhi, Brem, Steven, Wotoczek-Obadia, Marguerite, DelleDonne, Anthony, Patel, Nikunj, Obregon, Demian F., Crescentini, Robert, Abdullah, Laila, Coppola, Domenico, Rojiani, Amyn M., Crawford, Fiona, Sebti, Saïd M., Mullan, Michael·2004·Angiogenesis

DOI 10.1023/b:agen.0000037335.17717.bf

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Abstract

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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Authors: Paris, D., Townsend, K., Quadros, A., Humphrey, J., Sun, J., Brem, S., Wotoczek-Obadia, M., DelleDonne, A., Patel, N., Obregon, D. F., Crescentini, R., Abdullah, L., Coppola, D., Rojiani, A. M., Crawford, F., Sebti, S. M., & Mullan, M.
Affiliations: Roskamp Institute (US)
Moffitt Cancer Center (US)
Corresponding author: Mullan, Michael
ORCID: Paris, Daniel
Sun, Jiazhi
Brem, Steven
Patel, Nikunj
Abdullah, Laila
Coppola, Domenico
Rojiani, Amyn M.
Crawford, Fiona
Mullan, Michael
Venue: Angiogenesis
Publisher: Springer Science and Business Media LLC
Published: 2004-03
Volume: 7
Issue: 1
Pages: 75-85
ISSN: 0969-6970 (ISSN-L)
1573-7209
DOI: 10.1023/b:agen.0000037335.17717.bf
OpenAlex: W2599367511
Cited by: 148
References: 45
Citations by year: 2026: 3 · 2025: 7 · 2024: 9 · 2023: 8 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 6 · 2013: 7 · 2012: 7
FWCI: 2.60
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Angiogenesis (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: amyloid-beta, angiogenesis inhibition, β-sheet conformation, Alzheimer's disease, brain endothelial cells, capillary degeneration, tumor vascularization, glioblastoma, lung adenocarcinoma, tumor xenografts, anti-angiogenic peptides
MeSH terms: Animals, Cells, Cultured, Endothelium, Vascular, Female, Humans, Mice, Nude, Neoplasm Transplantation, Neoplasms, Experimental, Neovascularization, Pathologic, Peptide Fragments, Transplantation, Heterologous, Amyloid beta-Peptides, Treatment Outcome, Neovascularization, Physiologic, Angiogenesis Inhibitors, Middle Cerebral Artery, Cell Line, Tumor, Cell Proliferation, Mice

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Inhibition of Angiogenesis by Aβ Peptides

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