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


METHODS
Pharmacologic intervention in a surgically induced mouse model of endometriosis and endothelial migration assay.


METHODS
Animal research and laboratory facility.


METHODS
Eight-week-old, female C57BL/6 mice and human microvascular endothelial cells.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Short endostatin fragments may be promising as a new, nontoxic therapeutic strategy for the treatment of endometriosis without inhibition of normal estrous cycles.
Becker
Christian M
CM
Department of Surgery, Vascular Biology Program, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Sampson
David A
DA
Short
Sarah M
SM
Javaherian
Kashi
K
Folkman
Judah
J
D'Amato
Robert J
RJ
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy* / Q000378:metabolism; D043169:Endostatins / Q000138:chemical synthesis / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010060:Ovulation / Q000187:drug effects; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D010446:Peptide Fragments