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Endothelium
Journal of Endothelial Cell Research
Volume 11, 2004 - Issue 5-6
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Research Article

MS-818 Accelerates Mobilization of Endothelial Progenitor Cells and Differentiation to Endothelial Cells

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Pages 221-230 | Published online: 13 Jul 2009
 

Abstract

MS-818 that is a synthetic pyrimidine compound and shown to have neurotrophic actions, enhanced basic fibroblast growth factor (bFGF)-induced angiogenesis in vivo. However, the mechanism and whether MS-818 affects endothelial cells (ECs) directly is not known. Here, the authors investigated whether MS-818 alone could induce angiogenesis and tried to clarify the mechanism of neovascularization by MS-818 in terms of angiogenesis and vasculogenesis. The authors show that MS-818affects ECs directly and induces migration of and tube formation by ECs in vitro (angiogenesis). Furthermore, the authors demonstrate that MS-818 mobilizes endothelial progenitor cells (EPCs) from the bone marrow and potentiates their differentiation to ECs (vasculogenesis). The effect of MS-818 on the endothelial differentiation was further confirmed with an in vitro differentiation system using mouse embryonic stem cells. MS-818 activates the mitogen-activated protein kinase (MAPK) pathway but not the phosphoinositol 3-kinase (PI3K)-Akt pathway in ECs. These results indicate that MS-818, a synthetic compound, promotes both angiogenesis and vasculogenesis.

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