Peritoneal sclerosis is a major and serious complication in patients on 
long-term continuous ambulatory peritoneal dialysis (PD). The involvement of 
angiogenesis and proangiogenic factors such as vascular endothelial growth 
factor (VEGF)-A in progressing peritoneal sclerosis has been reported. We 
previously reported the therapeutic efficacy of endostatin peptide, a potent 
inhibitor of angiogenesis derived from type XVIII collagen, in a mouse diabetic 
nephropathy model. Here, we examined the therapeutic effect of endostatin 
peptide in preventing progression in a mouse peritoneal sclerosis model. Male 
ICR mice received intraperitoneal injections of chlorhexidine gluconate (CG) 
every other day to induce peritoneal sclerosis. Endostatin peptide (1 or 4 
mg/kg/day) was administered via subcutaneously implanted osmotic minipumps. 
Peritoneal sclerosis (day 24) was significantly suppressed by endostatin peptide 
in a dose-dependent manner. Peritoneal accumulation of type III collagen was 
significantly suppressed by endostatin peptide. Increase in the number of 
CD31(+) blood vessels, F4/80(+) monocyte/macrophage accumulation, and 
5-bromodeoxyuridine(+) proliferating cells was significantly inhibited by 
endostatin peptide. Increase in peritoneal expression of VEGF-A, profibrotic 
transforming growth factor-beta1, and alpha-smooth muscle actin was suppressed 
by endostatin peptide. Immunoreactivity for endogenous endostatin (whole 
molecule) and endostatin receptor alpha5beta1-integrin was increased and 
colocalized to CD31(+) blood vessels in the thickened peritonea of CG-injected 
mice. These results demonstrate the potential use of antiangiogenic endostatin 
peptide as a novel therapeutic agent in preventing peritoneal sclerosis, a 
severe complication in patients undergoing long-term PD.