title: Syndecan-4 deficiency limits neointimal formation after vascular injury by regulating vascular smooth muscle cell proliferation and vascular progenitor cell mobilization.
abstract: OBJECTIVE
  Syndecan-4 (Syn4) is a heparan sulfate proteoglycan and works as a coreceptor for various growth factors. We examined whether Syn4 could be involved in the development of neointimal formation in vivo.
  
  
  RESULTS
  Wild-type (WT) and Syn4-deficient (Syn4-/-) mice were subjected to wire-induced femoral artery injury. Syn4 mRNA was upregulated after vascular injury in WT mice. Neointimal formation was attenuated in Syn4-/- mice, concomitantly with the reduction of Ki67-positive vascular smooth muscle cells (VSMCs). Basic-fibroblast growth factor- or platelet-derived growth factor-BB-induced proliferation, extracellular signal-regulated kinase activation, and expression of cyclin D1 and Bcl-2 were impaired in VSMCs from Syn4-/- mice. To examine the role of Syn4 in bone marrow (BM)-derived vascular progenitor cells (VPCs) and vascular walls, we generated chimeric mice by replacing the BM cells of WT and Syn4-/- mice with those of WT or Syn4-/- mice. Syn4 expressed by both vascular walls and VPCs contributed to the neointimal formation after vascular injury. Although the numbers of VPCs were compatible between WT and Syn4-/- mice, mobilization of VPCs from BM after vascular injury was defective in Syn4-/- mice.
  
  
  CONCLUSIONS
  Syn4 deficiency limits neointimal formation after vascular injury by regulating VSMC proliferation and VPC mobilization. Therefore, Syn4 may be a novel therapeutic target for preventing arterial restenosis after angioplasty.
authors.affiliation: Department of Matrix Medicine, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikesue
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsui
authors.forename: Daichi
authors.initials: D
authors.lastname: Ohta
authors.forename: Keiko
authors.initials: K
authors.lastname: Danzaki
authors.forename: Koyu
authors.initials: K
authors.lastname: Ito
authors.forename: Masashi
authors.initials: M
authors.lastname: Kanayama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kurotaki
authors.forename: Junko
authors.initials: J
authors.lastname: Morimoto
authors.forename: Tetsuhito
authors.initials: T
authors.lastname: Kojima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
mesh_terms: D000818:Animals; D017209:Apoptosis; D000077214:Becaplermin; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006965:Hyperplasia; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D020574:Proto-Oncogene Proteins c-sis; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D053671:Syndecan-4 / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D017539:Tunica Intima / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D057772:Vascular System Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C530106:Ccnd1 protein, rat; D019394:Ki-67 Antigen; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020574:Proto-Oncogene Proteins c-sis; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; D016222:Fibroblast Growth Factor 2; C052617:Bcl2 protein, mouse; D019938:Cyclin D1; D000077214:Becaplermin; D048049:Extracellular Signal-Regulated MAP Kinases