Syndecan-4 Deficiency Limits Neointimal Formation After Vascular Injury by Regulating Vascular Smooth Muscle Cell Proliferation and Vascular Progenitor Cell Mobilization
Syndecan-4 Deficiency Limits Neointimal Formation After Vascular Injury by Regulating Vascular Smooth Muscle Cell Proliferation and Vascular Progenitor Cell Mobilization
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DOI：
10.1161/atvbaha.110.217703
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发表时间：
2011-05-01
影响因子：
8.7
通讯作者：
Uede, Toshimitsu
中科院分区：
文献类型：
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作者：
Ikesue, Masahiro;Matsui, Yutaka;Uede, Toshimitsu
Objective-Syndecan-4 (Syn4) 是一种硫酸乙酰肝素蛋白聚糖，可作为多种生长因子的辅助受体。我们检查了Syn4是否可能参与体内新内膜形成的发育。方法和结果-野生型(WT)和Syn4缺陷型(Syn4(-/-))小鼠受到线诱导的股动脉损伤。 WT 小鼠血管损伤后 Syn4 mRNA 上调。 Syn4(-/-) 小鼠的新内膜形成减弱，同时伴随着 Ki67 阳性血管平滑肌细胞 (VSMC) 的减少。 Syn4(-/-) 小鼠的 VSMC 中碱性成纤维细胞生长因子或血小板衍生生长因子 BB 诱导的增殖、细胞外信号调节激酶激活以及细胞周期蛋白 D1 和 Bcl-2 的表达受损。为了研究 Syn4 在骨髓 (BM) 来源的血管祖细胞 (VPC) 和血管壁中的作用，我们通过用 WT 或 Syn4(-/-) 小鼠的 BM 细胞替换 WT 和 Syn4(-/-) 小鼠的 BM 细胞来产生嵌合小鼠。血管壁和 VPC 表达的 Syn4 有助于血管损伤后新内膜的形成。尽管WT和Syn4(-/-)小鼠之间的VPC数量相容，但血管损伤后从BM中动员VPC的能力在Syn4(-/-)小鼠中存在缺陷。 结论：Syn4缺陷通过调节VSMC增殖和VPC动员来限制血管损伤后新内膜的形成。因此，Syn4可能是预防血管成形术后动脉再狭窄的新治疗靶点。 （动脉硬化血栓 Vasc Biol.2011；31：1066-1074。）
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. (Arterioscler Thromb Vasc Biol. 2011;31:1066-1074.)