Angiopoietin-1 inhibits doxorubicin-induced human umbilical vein endothelial cell death by modulating fas expression and via the PI3K/Akt pathway.

Angiopoietin-1 inhibits doxorubicin-induced human umbilical vein endothelial cell death by modulating fas expression and via the PI3K/Akt pathway.
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DOI：
10.1080/10623320490904115
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发表时间：
2004-09
期刊：
Endothelium : journal of endothelial cell research
影响因子：
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通讯作者：
D. Yin;Chuanful Li;R. Kao;T. Ha;G. Krishnaswamy;Matthew P. Fitzgerald;C. Stuart
D. Yin;Chuanful Li;R. Kao;T. Ha;G. Krishnaswamy;Matthew P. Fitzgerald;C. Stuart
中科院分区：
其他
文献类型：
--
作者：
D. Yin;Chuanful Li;R. Kao;T. Ha;G. Krishnaswamy;Matthew P. Fitzgerald;C. Stuart

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血管生成素-1 （ang1）在血管形成过程中对血管的成熟至关重要。除了血管生成，最近的出版物表明Ang-1也是内皮细胞的有效存活因子；然而，途径的机制仍然难以捉摸。阿霉素（DOX）是一种强效抗癌药物，但由于其心脏毒性，其使用受到严格限制。作者在这里报告了Ang-1抑制dox诱导的人脐静脉内皮细胞（HUVECs）的细胞死亡。有趣的是，dox诱导的Fas （CD95/APO-1）和Fas配体表达上调可被Ang-1阻断，表明Ang-1在dox诱导的Fas和Fas配体表达中起关键作用。此外，在该模型系统中，细胞死亡的预防似乎依赖于磷脂酰肌醇3-激酶(PI3K)/Akt的激活，因为Ang-1无法抑制dox诱导的细胞死亡，而PI3K/Akt通路被PI3K抑制剂LY294002阻断。此外，Ang-1通过PI3K/Akt抑制dox诱导的p53上调。因此，Ang-1通过Fas和PI3K/ akt介导的途径是dox诱导的细胞死亡的有效抑制剂。
Angiopoietin-1 (Ang-1) is essential for the maturation of blood vessels during vasculogenesis. Besides angiogenesis, recent publications indicate that Ang-1 is also a potent survival factor for endothelial cells; however, the mechanisms by which pathways remain elusive. Doxorubicin (DOX) is a powerful anticancer drug, but its use is severely restricted by its cardiotoxicity. The authors report here that Ang-1 inhibits DOX-induced cell death in human umbilical vein endothelial cells (HUVECs). Interestingly, the DOX-induced up-regulation in Fas (CD95/APO-1) and Fas ligand expression could be blocked by Ang-1, indicating a pivotal role of Ang-1 in DOX-induced Fas and Fas ligand expression. In addition, the prevention of cell death in this model system seems to be dependent on the activation of phosphatidylinositol 3-kinase (PI3K)/Akt, as Ang-1 fails to inhibit DOX-induced cell death while PI3K/Akt pathway was blocked by the PI3K inhibitor LY294002. Moreover, Ang-1 inhibits DOX-induced up-regulation of p53 through PI3K/Akt. Therefore, Ang-1 is a potent inhibitor for DOX-induced cell death through Fas and PI3K/Akt-mediated pathways.