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Abstract: SA-PO957

Protective Effect of COMP-Angiopoietin 1 on Peritoneal Vascular Permeability and Peritoneal Transport Function in Uremic Peritoneal Dialysis Rats

Session Information

Category: Dialysis

  • 703 Dialysis: Peritoneal Dialysis

Author

  • Shi, Yuanyuan, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Background

The angiopoietin-1 (Ang-1)/Tie-2 signaling pathway plays a crucial role in the maintenance of vascular stabilization and permeability.

Methods

Thirty-six male Sprague-Dawley rats were randomly assigned to the sham operation group, uremia group or uremia+PD group (each n=12). Then, COMP-Ang-1 adenovirus or vehicle adenovirus was injected into twenty other uremic PD rats via the tail vein (each n=10). A peritoneal equilibration test (PET) was performed to evaluate peritoneal transport function before the rats were euthanized. Peritoneal vascular permeability was assessed by measuring FITC-dextran (4 kDa) and FITC-BSA (69 kDa) leakage. The pericyte coverage rate was quantified by anti-CD31 and anti-Desmin immunofluorescence staining. Expression of endothelial junction proteins and Ang-1/Tie-2 signaling were examined by western blotting. The levels of proinflammatory adhesion molecules and cytokines in the peritoneum were measured by real-time quantitative polymerase chain reaction (PCR).

Results

Compared to the sham controls, uremic rats were characterized by decreased pericyte coverage, downregulated endothelial junction protein expression and increased FITC-BSA and FITC-dextran leakage, accompanied by increased levels of proinflammatory adhesion molecules and cytokines, increased D/Pcr and decreased ultrafiltration. After infusion of PDF for 4 weeks, more marked changes were noted. Peritoneal Ang-1 protein expression and Tie-2 phosphorylation were significantly lower in uremic rats than in control rats and were further significantly reduced in uremia+PD rats. After COMP-Ang-1 administration, phosphorylation of the Tie-2 receptor was significantly increased. Treatment with COMP-Ang-1 also significantly enhanced pericyte coverage, upregulated endothelial junctions expression and inhibited the leakage of FITC-BSA and FITC-dextran from the peritoneal vasculature induced during PD therapy; these changes were accompanied by reduced peritoneal tissue levels of proinflammatory adhesion molecules and cytokines, decreased D/Pcr and increased ultrafiltration.

Conclusion

COMP-Ang-1 exerts a protective effect against damage-induced peritoneal vascular permeability and inflammation at least in part by enhancing pericyte coverage and endothelial junction protein expression, which subsequently significantly improves peritoneal transport function.