Effect of fucoidan on fibroblast growth factor-2-induced angiogenesis in vitro
Effect of fucoidan on fibroblast growth factor-2-induced angiogenesis in vitro
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DOI：
10.1016/s0049-3848(02)00136-6
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发表时间：
2002-05-15
影响因子：
7.5
通讯作者：
Fischer, AM
中科院分区：
文献类型：
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作者：
Matou, S;Helley, D;Fischer, AM
岩藻聚糖是从褐藻中提取的硫酸化多糖。纯化的岩藻依聚糖组分在兔体内表现出与肝素相同的静脉抗血栓形成活性，但具有较低的抗凝作用。由于其肝素样结构，我们假设岩藻依聚糖可能调节肝素结合血管生成生长因子的活性。因此，我们研究了其效果，在抗血栓浓度，对成纤维细胞生长因子（FGF）-2诱导的人脐静脉内皮细胞的增殖和分化。通过研究已知由FGF-2调节并参与血管生成的表面蛋白（即整合素、粘附分子）的表达，并通过定量由重建基底膜上形成的血管管界定的闭合区域，评价岩藻依聚糖对内皮细胞分化的影响。褐藻糖胶对FGF-2的促有丝分裂活性无调节作用，但能显著增加FGF-2诱导的肾小管结构密度。岩藻依聚糖单独增加α（6）整合素亚基表达，仅部分组织化管状结构。在FGF-2的存在下，岩藻依聚糖增强α（6）、β（1）和PECAM-1，并抑制α（v）β（3）整联蛋白的表达。肝素在这些系统中没有作用。岩藻依聚糖对α（6）表达的影响最显著，单克隆抗α（6）抗体可消除管形成。岩藻依聚糖和FGF-2对α 6表达的影响被单克隆抗FGF-2抗体显著降低，表明岩藻依聚糖主要通过FGF-2起作用。这些结果表明，在抗血栓浓度下，与肝素相反，岩藻依聚糖可以增强FGF-2诱导的血管管形成，并调节参与血管生成的表面蛋白（主要是α（6））的表达。(C)2002爱思唯尔科技有限公司。保留所有权利。
Fucoidans are sulfated polysaccharides extracted from brown marine algae. A purified fucoidan fraction exhibits the same venous antithrombotic activity as heparin in rabbits, but with a lower anticoagulant effect. Because of its heparin-like structure, we postulated that fucoidan might modulate heparin-binding angiogenic growth factor activity. We thus studied its effect, at antithrombotic concentrations, on fibroblast growth factor (FGF)-2-induced proliferation and differentiation of human umbilical vein endothelial cells. The fucoidan effect on endothelial cell differentiation was evaluated by studying the expression of surface proteins (i.e. integrin, adhesion molecule) known to be modulated by FGF-2 and involved in angiogenesis, and by quantifying closed areas delimited by vascular tubes formed on reconstituted basement membrane. Fucoidan had no modulatory effect on the mitogenic activity of FGF-2, but significantly increased tubular structure density induced by FGF-2. Fucoidan alone increased alpha(6) integrin subunit expression with only partially organized tubular structure. In the presence of FGF-2, fucoidan enhanced alpha(6), beta(1) and PECAM-1 and inhibited alpha(v)beta(3) integrin expression. Heparin had no effect in these systems. The most striking effect of fucoidan was observed on alpha(6) expression and tube formation was abolished by monoclonal anti-alpha(6) antibodies. Fucoidan plus FGF-2 effect on alpha(6) expression was markedly decreased by monoclonal anti-FGF-2 antibodies, indicating that fucoidan acts mainly via FGF-2. These results show that, at antithrombotic concentrations, contrary to heparin, fucoidan can enhance vascular tube formation induced by FGF-2 with a modulation of the expression of surface proteins (mainly alpha(6)) involved in angiogenesis. (C) 2002 Elsevier Science Ltd. All rights reserved.