FGF-2 overexpression opposes the beta amyloid toxic injuries to the vascular endothelium.

Recent evidences suggest that Abeta peptides modulate endothelial cell (EC) functions. At low concentrations, Abeta1-40 enhances the pro-angiogenic activity of FGF-2, whereas deposition of excess Abeta causes EC dysfunction and cerebral amyloid angiopathy (CAA). We investigated whether FGF-2 attenuates EC dysfunction caused by pathological Abeta levels. We studied Abeta1-40 on ...
EC survival, as well as on signals responsible of their angiogenic phenotype. At 5-50 microM Abeta1-40 reduced EC population, caused apoptosis, downregulated FGF-2 production, inhibited FGF-2 binding to heparin, and FGFR1 phosphorylation. Toxic effects were owing to lack of FGF-2 stimulation, as EC overexpressing FGF-2 displayed extraordinary resistance to Abeta1-40 injuries. The FGF-2 mechanism responsible for reversing damages, involves the downstream enhancement of Akt, a pathway independent of eNOS activation. In conclusion, we demonstrate that FGF-2 protects EC from the effects of excess Abeta1-40, suggesting that it may attenuate the consequences of Abeta deposition in pathologies as CAA.
Mesh Terms:
Amyloid beta-Peptides, Animals, Blotting, Western, CHO Cells, Caspase 3, Caspases, Cell Survival, Cells, Cultured, Cricetinae, Cricetulus, Endothelial Cells, Endothelium, Vascular, Enzyme Activation, Fibroblast Growth Factor 2, Humans, Mice, Nitric Oxide Synthase Type III, Peptide Fragments, Phosphorylation, Proto-Oncogene Proteins c-akt, Vascular Endothelial Growth Factor A
Cell Death Differ
Date: Jul. 01, 2006
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