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

Recent evidences suggest that A beta peptides modulate endothelial cell (EC) functions. At low concentrations, A beta(1-40) enhances the pro-angiogenic activity of FGF-2, whereas deposition of excess A beta causes EC dysfunction and cerebral amyloid angiopathy (CAA). We investigated whether FGF-2 attenuates EC dysfunction caused by pathological A beta levels. We studied A beta(1-40) on EC survival, as well as on signals responsible of their angiogenic phenotype. At 5-50 mu M A beta(1-40) 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 A beta 1-40 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 A beta 1-40, suggesting that it may attenuate the consequences of Ab deposition in pathologies as CAA.