FGF-2 overexpression opposes the beta amyloid toxic injuries to the vascular endothelium
FGF-2 overexpression opposes the beta amyloid toxic injuries to the vascular endothelium
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DOI：
10.1038/sj.cdd.4401803
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发表时间：
2006-07-01
影响因子：
12.4
通讯作者：
Ziche, M.
中科院分区：
文献类型：
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作者：
Donnini, S.;Cantara, S.;Ziche, M.
最近的证据表明，A β肽调节内皮细胞（EC）的功能。在低浓度下，A β（1-40）增强FGF-2的促血管生成活性，而过量A β的沉积导致EC功能障碍和脑淀粉样血管病（CAA）。我们研究了FGF-2是否减弱病理性A β水平引起的EC功能障碍。我们研究了A β（1-40）对EC存活的影响，以及对负责其血管生成表型的信号的影响。在5-50 μ M下，A β（1-40）减少EC群体，引起细胞凋亡，下调FGF-2的产生，抑制FGF-2与肝素的结合和FGFR 1磷酸化。毒性作用是由于缺乏FGF-2刺激，因为过表达FGF-2的EC对A β 1-40损伤表现出非凡的抗性。负责逆转损伤的FGF-2机制涉及Akt的下游增强，Akt是一种独立于eNOS活化的途径。总之，我们证明FGF-2保护EC免受过量A β 1-40的影响，这表明它可能会减弱CAA病理学中Ab沉积的后果。
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.