title: N-acetyl-seryl-aspartyl-lysyl-proline stimulates angiogenesis in vitro and in vivo.
abstract: 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.
authors.affiliation: Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 W. Grand Blvd., Detroit, MI 48202-2689, USA.
authors.forename: Dahai
authors.initials: D
authors.lastname: Wang
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Carretero
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Yang
authors.forename: Nour-Eddine
authors.initials: NE
authors.lastname: Rhaleb
authors.forename: Yun-He
authors.initials: YH
authors.lastname: Liu
authors.forename: Tang-Dong
authors.initials: TD
authors.lastname: Liao
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yang
mesh_terms: 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*
chemical_list: D009842:Oligopeptides; D004247:DNA; C058504:goralatide