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PMID: 15256375 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

N-acetyl-seryl-aspartyl-lysyl-proline stimulates angiogenesis in vitro and in vivo.

American journal of physiology. Heart and circulatory physiology ·Vol. 287 ·No. 5 ·2004-11-00 ·Pages H2099-105

Wang D, Carretero OA, Yang XY, Rhaleb NE, Liu YH, Liao TD, Yang XP

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.

MeSH Terms
Animals Capillaries/drug effects,growth & development Cell Line, Transformed Cell Movement/drug effects Corneal Neovascularization/physiopathology Coronary Vessels/drug effects,growth & development DNA/biosynthesis Endothelial Cells Mice Mice, Inbred BALB C Neovascularization, Physiologic/drug effects Oligopeptides/pharmacology
Chemicals
Oligopeptides DNA goralatide
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wang Dahai
Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 W. Grand Blvd., Detroit, MI 48202-2689, USA.
Carretero Oscar A
Yang Xiao-Yi
Rhaleb Nour-Eddine
Liu Yun-He
Liao Tang-Dong
Yang Xiao-Ping
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Article Info
Journal
American journal of physiology. Heart and circulatory physiology
Abbr.
Am J Physiol Heart Circ Physiol
ISSN
0363-6135
Published
2004-11-00
Epub
2004-00-15
Pages
H2099-105
Language
English
Region
United States
NLM ID
100901228
PMCID
PMC6824423
Subset
IM
Grants
NHLBI NIH HHS · R01 HL071806 · United States
NHLBI NIH HHS · HL-28982 · United States
NHLBI NIH HHS · HL-71806 · United States
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