N-acetyl-seryl-aspartyl-lysyl-proline stimulates angiogenesis in vitro and in vivo.
N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a natural inhibitor of pluripotent hematopoietic stem cell proliferation, has been suggested as capable of promoting an angiogenic response. We studied whether Ac-SDKP stimulates endothelial cell proliferation, migration, and tube formation; enhances angiogenic response in the rat cornea after implantation of a tumor spheroid; and increases capillary density in rat hearts with myocardial infarction (MI). In vitro, an immortal BALB/c mouse aortic endothelial 22106 cell line was used to determine the effects of Ac-SDKP on endothelial cell proliferation and migration and tube formation. In vivo, a 9L-gliosarcoma cell spheroid (250-300 microm in diameter) was implanted in the rat cornea and vehicle or Ac-SDKP (800 microg.kg(-1).day(-1) ip) infused via osmotic minipump. Myocardial capillary density was studied in rats with MI given either vehicle or Ac-SDKP. We found that Ac-SDKP 1) stimulated endothelial cell proliferation and migration and tube formation in a dose-dependent manner, 2) enhanced corneal neovascularization, and 3) increased myocardial capillary density. Endothelial cell proliferation and angiogenesis stimulated by Ac-SDKP could be beneficial in cardiovascular diseases such as hypertension and MI. Furthermore, because Ac-SDKP is mainly cleaved by ACE, it may partially mediate the cardioprotective effect of ACE inhibitors.
Wang
Dahai
D
Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 W. Grand Blvd., Detroit, MI 48202-2689, USA.
Carretero
Oscar A
OA
Yang
Xiao-Yi
XY
Rhaleb
Nour-Eddine
NE
Liu
Yun-He
YH
Liao
Tang-Dong
TD
Yang
Xiao-Ping
XP
D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D016510:Corneal Neovascularization / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000254:growth & development; D004247:DNA / Q000096:biosynthesis; D042783:Endothelial Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*
D009842:Oligopeptides; D004247:DNA; C058504:goralatide