Syndecan-4 deficiency limits neointimal formation after vascular injury by regulating vascular smooth muscle cell proliferation and vascular progenitor cell mobilization

Masahiro Ikesue, Yutaka Matsui, Daichi Ohta, Keiko Danzaki, Koyu Ito, Masashi Kanayama, Daisuke Kurotaki, Junko Morimoto, Tetsuhito Kojima, Hiroyuki Tsutsui, Toshimitsu Uede

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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. Methods and 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. Conclusion- 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.

Original languageEnglish
Pages (from-to)1066-1074
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume31
Issue number5
DOIs
Publication statusPublished - 2011 May
Externally publishedYes

Keywords

  • growth factors
  • neointimal hyperplasia
  • vascular injury
  • vascular progenitor cells
  • vascular smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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