Short synthetic endostatin peptides inhibit endothelial migration in vitro and endometriosis in a mouse model

ObjectiveTo determine the active peptide regions inside the angiogenesis inhibitor endostatin that can inhibit endothelial migration in vitro and also inhibit endometriosis in a mouse model.DesignPharmacologic intervention in a surgically induced mouse model of endometriosis and endothelial migration assay.SettingAnimal research and laboratory facility.Subject(s)Eight-week-old, female C57BL/6 mice and human microvascular endothelial cells.Intervention(s)Eight overlapping synthetic peptides were tested for inhibitory potential on endothelial migration in vitro. The peptides with significant activity then were given for 4 weeks to mice after implantation of autologous endometrium.Main Outcome Measure(s)Inhibition of vascular endothelial growth factor–induced endothelial migration for in vitro studies. In vivo studies examined the growth rate of endometriotic lesions after 4 weeks of treatment, as well as the effect on estrous cycling and ovulation as assessed by corpus luteum formation.Result(s)The N-terminal mP-1 peptide and the internal mP-6 peptide inhibited endothelial migration in a dose-dependent manner. Additionally, both synthetic peptides suppressed growth of endometriotic lesions significantly in vivo. However, estrous cycling and corpus luteum formation were normal in both groups.Conclusion(s)Short endostatin fragments may be promising as a new, nontoxic therapeutic strategy for the treatment of endometriosis without inhibition of normal estrous cycles.