Beta amyloid angiogenic activity in vitro and in vivo.
Angiogenesis has been suggested as a direct contributor to Alzheimer's disease (AD) pathology. The major pathological hallmarks of AD are the presence of neurofibrillary tangles and, beta-amyloid plaques associated with activated microglia, astrocytes, degenerating neurons and vascular toxicity. In this study, Abeta1-40 and Abeta1-42 peptides, both components of the senile plaques in AD, were used to study their angiogenic activity in vitro, by using normal human cerebral endothelial cells (HCECs), and in vivo, by using the chick embryo chorioallantoic membrane (CAM) assay. Results showed that both peptides stimulate in vitro endothelial cell proliferation, chemotaxis and morphogenesis in Matrigel. Moreover, by using the aorta ring assay, both peptides stimulated the formation of capillary-like structures. An angiogenic response was induced in the CAM assay, similar to that induced by fibroblast growth factor-2 (FGF-2), a well-known angiogenic cytokine. Overall, these data support the hypothesis that Abeta peptides may contribute to angiogenesis occurring in AD and suggest that limiting the pro-angiogenic activity of Abeta peptides may therefore provide a useful target to control angiogenesis associated to AD and therefore limit the disease progression.
Boscolo
Elisa
E
Department of Biology, University of Padua, Padua, Italy.
Folin
Marcella
M
Nico
Beatrice
B
Grandi
Claudio
C
Mangieri
Domenica
D
Longo
Vito
V
Scienza
Renato
R
Zampieri
Paolo
P
Conconi
Maria Teresa
MT
Parnigotto
Pier Paolo
PP
Ribatti
Domenico
D
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000502:physiology; D001011:Aorta / Q000187:drug effects; D001921:Brain / Q000098:blood supply; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000209:etiology*; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)