Angiopoietin-1 Inhibits Doxorubicin-Induced Human Umbilical Vein Endothelial Cell Death by Modulating FAS Expression and via the P13K/Akt Pathway
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.
Yin, Deling; Li, Chuanfu; Kao, Race L.; Ha, Tuanzhu; Krishnaswamy, Guha; Fitzgerald, Matthew; and Stuart, Charles A.. 2004. Angiopoietin-1 Inhibits Doxorubicin-Induced Human Umbilical Vein Endothelial Cell Death by Modulating FAS Expression and via the P13K/Akt Pathway. Endothelium: Journal of Endothelial Cell Research. Vol.11(5-6). 247-252. https://doi.org/10.1080/10623320490904115 PMID: 15763944 ISSN: 1062-3329