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首页> 外文期刊>Journal of Cellular Physiology >Inhibition of rat smooth muscle cell adhesion and proliferation by non-anticoagulant heparins.
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Inhibition of rat smooth muscle cell adhesion and proliferation by non-anticoagulant heparins.

机译:抑制大鼠平滑肌细胞粘附和扩散通过non-anticoagulant肝素。

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Heparin is a well established growth inhibitor of arterial smooth muscle cells (SMCs) both in animal models and in vitro. Even though the cellular mechanisms involved in the anti-proliferative properties of heparin are being resolved, the structural requirements for the biological effects of heparin are not known in detail. Here, we have studied the effect of chemically modified heparins of different molecular weights and anticoagulant activities on proliferation and adhesion of rat aortic SMCs in vitro. The effects of native heparin (NH) and chemically modified heparins were examined after stimulation with fetal calf serum (FCS), platelet-derived growth factor BB (PDGF BB), basic fibroblast growth factor (bFGF), and heparin-binding epidermal growth factor (hbEGF) with respect to DNA synthesis and expression of phosphorylated and activated mitogen-activated protein kinase (pERK1 and 2). In a similar manner as NH, the modified heparins were capable of inhibiting activation of ERK1 and 2 and DNA synthesis induced by FCS and hbEGF whereas the modified heparins potentiated the mitogenic effect of bFGF and no compound affected PDGF BB-induced ERK activity and SMC growth. In contrast, cell adhesion to fibronectin was inhibited by NH and modified heparins in a size-dependent manner with the lowest effect by the smallest compound. The results show that heparins with varying anticoagulant activities and molecular weights but with similar sulfate content can retain anti-proliferative properties while the effect on some other biological processes such as cell adhesion is lost. Possibly, such chemical alterations may yield useful substances for the prevention of SMC proliferation after arterial injury. J. Cell. Physiol. 193: 365-372, 2002. Copyright 2002 Wiley-Liss, Inc.
机译:肝素是一种被广泛接受的生长抑制剂动脉平滑肌细胞(smc)动物模型和体外。参与细胞机制anti-proliferative肝素的性质被解决,结构要求肝素的生物效应是不清楚在细节。肝素不同的化学修改分子量和抗凝活动扩散和鼠主动脉smc的附着力体外。化学改性后肝素被检查刺激与胎牛血清(FCS),血小板源生长因子BB (PDGF BB),基本成纤维细胞生长因子(bFGF)heparin-binding表皮生长因子(hbEGF)对DNA合成和表达磷酸化,激活增殖作用蛋白激酶(pERK1和2),以类似的方式NH,修改后的肝素的能力抑制激活ERK1和2和DNA合成FCS和hbEGF而引起的修改后的肝素强促有丝分裂的bFGF和复合影响PDGF的效果BB-induced ERK活性和SMC的增长。相反,纤连蛋白是细胞粘附肝素在抑制NH和修改尺度依赖的方式最低的效果最小的化合物。肝素不同抗凝剂的活动和分子量,但类似的硫酸内容可以保留anti-proliferative属性而对其他生物的影响过程,如细胞粘附丢失。可能,这种化学变化可能屈服预防SMC的有用物质动脉损伤后扩散。杂志。193:365 - 372年,2002年。Wiley-Liss公司。

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