Soluble Tie2 fusion protein decreases peritoneal angiogenesis in uremic rats.

Angiogenesis is considered to be one of the most common mechanisms leading to ultrafiltration failure (UFF) in long-term peritoneal dialysis (PD) patients. The angiopoietin (Ang)/Tie system was found to play a role in the initiation of pathological neoangiogenesis and is also involved in peritoneal angiogenesis caused by peritoneal fluid. This aim of this study was to investigate the effects of the soluble Tie2 fusion protein (sTie2/Fc) on peritoneal angiogenesis in PD-treated uremic rats. The rats were divided into 6 groups: normal, sham surgery, uremic rats without PD, uremic PD-treated rats, uremic rats treated with PD and sTie2/Fc (0.25 µg/100 g) and uremic rats treated with PD and sTie2/Fc (0.5 µg/100 g). PD rats were treated once a day for 28 days prior to testing. Real-time polymerase chain reaction (RT-PCR) or tissue immunohistochemical staining was used to detect Ang-2 mRNA or protein expression in the peritoneal tissues of each group. The microvessel density (MVD) of the peritoneum was detected and quantified by immunohistochemical staining using the anti-CD34 antibody. Compared with the control group, Ang-2 mRNA and protein expression was significantly upregulated in the uremic and PD groups (P<0.05). MVD in the experimental group increased compared with the control group. sTie2/Fc treatment decreased the levels of Ang-2 mRNA and protein expression (P<0.05) in a dose-dependent manner and decreased PD-induced MVD in the peritoneum. In conclusion, angiogenesis of the peritoneum induced by PD was inhibited using sTie2/Fc in a uremic rat model.

A single local injection of recombinant VEGF receptor 2 but not of Tie2 inhibits retinal neovascularization in the mouse.

PURPOSE: The purpose of this study was to develop pharmacological therapeutic alternatives for ischemia-induced proliferative retinopathy. METHODS: C57BL/6J mice were placed in 76% oxygen on postnatal day 7 (P7) for 5 days. On P12 recombinant, chimeric vascular endothelial growth factor (sVEGF-R2) or sTie2 was injected intravitreally in one eye. The fellow eye received a control injection. On P17, retinal wholemounts were prepared after perfusion with fluorescein-dextran to quantify the retinopathy. RESULTS: A single intravitreal injection of sVEGF-R2 reduced pathologic vascular changes significantly (p = 0.02). No significant effect was observed after intravitreal application of sTie2 (p = 0.07), although Ang-2 was upregulated in control animals without treatment as neovascularization developed and Ang-1 was constantly transcribed (ratio PCR). CONCLUSIONS: sVEGF-R2 interferes with VEGF signaling via VEGF-R2 receptor. Thus, local application of soluble receptors for angiogenic factors is a possible therapy for proliferative retinopathy. Receptors with a wide range of ligands might prove more useful for local application than those binding few or antagonistic ligands.