Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell
Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell
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DOI：
10.1161/01.cir.0000018622.84402.ff
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发表时间：
2002-06-18
期刊：
影响因子：
37.8
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Arita, Y;Kihara, S;Matsuzawa, Y
背景：血管平滑肌细胞增殖在动脉粥样硬化的发生发展中起重要作用。我们之前报道过脂联素，一种脂肪细胞特异性血浆蛋白，在人损伤动脉中积累，抑制内皮炎症反应以及巨噬细胞向泡沫细胞的转化。本研究探讨了脂联素对人主动脉平滑肌细胞增殖和迁移的影响。方法与结果：采用[H-3]胸腺嘧啶摄取法和细胞数法检测hasmc增殖情况。采用博伊登室进行细胞迁移试验。脂联素的生理浓度显著抑制血小板衍生生长因子(PDGF)-BB刺激的HASMCs的增殖和迁移。脂联素特异性结合I-125-PDGF-BB并显著抑制I-125-PDGF-BB与HASMCs的关联，但未观察到对I-125-PDGF-AA或i -125-肝素结合的表皮生长因子（EGF）样生长因子（HB-EGF）与HASMCs结合的影响。免疫印迹分析脂联素强烈且剂量依赖性地抑制PDGF- bb诱导的p42/44细胞外信号相关激酶（ERK）磷酸化和PDGF β受体自磷酸化。脂联素也以剂量依赖的方式降低PDGF- aa刺激或hb -EGF刺激的ERK磷酸化，而不影响PDGF- a受体或EGF受体的自磷酸化。结论脂肪细胞源性血浆蛋白脂联素通过与PDGF-BB直接结合强烈抑制HASMC增殖和迁移，普遍抑制生长因子刺激的HASMC ERK信号，提示脂联素在血管重构中起调节作用。
Background-Vascular smooth muscle cell proliferation plays an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipocyte-specific plasma protein, accumulated in the human injured artery and suppressed endothelial inflammatory response as well as macrophage-to-foam cell transformation. The present study investigated the effects of adiponectin on proliferation and migration of human aortic smooth muscle cells (HASMCs).Methods and Results-HASMC proliferation was estimated by [H-3] thymidine uptake and cell number. Cell migration assay was performed using a Boyden chamber. Physiological concentrations of adiponectin significantly suppressed both proliferation and migration of HASMCs stimulated with platelet-derived growth factor (PDGF)-BB. Adiponectin specifically bound to I-125-PDGF-BB and significantly inhibited the association of I-125-PDGF-BB with HASMCs, but no effects were observed on the binding of I-125-PDGF-AA or I-125-heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) to HASMCs. Adiponectin strongly and dose-dependently suppressed PDGF-BB-induced p42/44 extracellular signal-related kinase (ERK) phosphorylation and PDGF beta-receptor autophosphorylation analyzed by immunoblot. Adiponectin also reduced PDGF-AA-stimulated or HB-EGF-stimulated ERK phosphorylation in a dose-dependent manner without affecting autophosphorylation of PDGF a-receptor or EGF receptor.Conclusions-The adipocyte-derived plasma protein adiponectin strongly suppressed HASMC proliferation and migration through direct binding with PDGF-BB and generally inhibited growth factor-stimulated ERK signal in HASMCs, suggesting that adiponectin acts as a modulator for vascular remodeling.