Enhanced ability of heparin-carrying polystyrene (HCPS) to bind to heparin-binding growth factors and to inhibit growth factor-induced endothelial cell growth
Enhanced ability of heparin-carrying polystyrene (HCPS) to bind to heparin-binding growth factors and to inhibit growth factor-induced endothelial cell growth
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DOI：
10.1093/oxfordjournals.jbchem.a022672
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发表时间：
2000-05-01
影响因子：
2.7
通讯作者：
Kurita, A
中科院分区：
文献类型：
--
作者：
Ishihara, M;Ono, K;Kurita, A
载肝素聚苯乙烯（HCPS）由富含三硫酸化二糖结构的低分子量肝素链连接到聚苯乙烯核心组成。在本研究中，将不同分子量的HCPSs与肝素结合生长因子VEGF（165）、FGF-2和HGF之间的相互作用与相同因子与天然肝素、高碘酸盐氧化肝素（IO 4-肝素）和高碘酸盐氧化碱性降解肝素（IO 4-LMW-肝素）之间的相互作用进行了比较。每种生长因子对肝素-琼脂糖珠（肝素珠）的盲态被HCPS以分子量依赖性方式比天然肝素或改性肝素更强烈地抑制，表明HCPS与这些生长因子之间的相互作用更强。HCPSs还以分子量依赖性方式抑制肝素结合生长因子诱导的内皮细胞生长，比天然或修饰的肝素更强。然而，HCPS不抑制VEGF的促有丝分裂活性（121），其具有非肝素结合性质。因此，HCPSs表现出增强的能力，与研究的肝素结合生长因子的每一个相互作用，并抑制肝素结合生长因子诱导的内皮细胞增殖的分子量依赖性的方式。这些作用可能归因于HCPSs的肝素聚集效应。
Heparin-carrying polystyrene (HCPS) consists of low-molecular-weight heparin chains enriched in trisulfated disaccharide structures linked to a polystyrene core. In this study, the interactions between HCPSs of various molecular weights and heparin-binding growth factors, VEGF(165), FGF-2, and HGF, were compared to the interactions of the same factors with native heparin, periodate-oxidized heparin (IO4-heparin) and periodate-oxidized alkaline-degraded heparin (IO4-LMW-heparin). The blinding of each growth factor to heparin-agarose beads (heparin-beads) was more strongly inhibited by HCPSs in a molecular weight-dependent manner than by native heparin or the modified heparins, indicating a stronger interaction between HCPS and these growth factors. HCPSs also inhibit heparin-binding growth factor-induced endothelial cell growth in a molecular weight-dependent manner much more strongly than the native or modified heparins. However, HCPSs did not inhibit the mitogenic activity of VEGF(121), which has a non-heparin-binding nature. Thus, HCPSs exhibit enhanced abilities to interact with each of the heparin-binding growth factors studied and to inhibit heparin-binding growth factor-induced endothelial cell proliferation in a molecular weight-dependent manner. These effects might be ascribed to the heparin-clustering effect of HCPSs.