Syndecan-4 deficiency limits neointimal formation after vascular injury by regulating vascular smooth muscle cell proliferation and vascular progenitor cell mobilization.
Arterioscler Thromb Vasc Biol
; 31(5): 1066-74, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21330609
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 ANDRESULTS:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
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Movimento Celular
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Túnica Íntima
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Miócitos de Músculo Liso
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Proliferação de Células
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Sindecana-4
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Lesões do Sistema Vascular
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Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article