title: MS-818 accelerates mobilization of endothelial progenitor cells and differentiation to endothelial cells.
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-818 affects 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.
authors.affiliation: Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Seiryo-machi, Sendai, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kanemura
authors.forename: Mayumi
authors.initials: M
authors.lastname: Abe
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Ueda
authors.forename: Minoru
authors.initials: M
authors.lastname: Ueki
authors.forename: Akira
authors.initials: A
authors.lastname: Awaya
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt; D011743:Pyrimidines / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*
chemical_list: C096499:MS 818; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3