Kohno M, Yokokawa K, Yasunari K, Minami M, Kano H, Mandal A K, Yoshikawa J
The First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
Metabolism. 1998 Sep;47(9):1065-9. doi: 10.1016/s0026-0495(98)90279-7.
Heparin, an anticoagulant, has been shown to reduce neointimal proliferation and restenosis following vascular injury in experimental studies, but the clinical trials of heparin in coronary balloon angioplasty have been negative. The current study, therefore, examined the effect of heparin on basal or stimulated migration by serum and platelet-derived growth factor (PDGF)-BB in cultured human coronary artery smooth muscle cells (SMCs) by Boyden's chamber method. In addition, the reversibility of the heparin effect on human coronary artery SMC migration was examined. Fetal calf serum (FCS) and PDGF-BB stimulated SMC migration in a concentration-dependent manner. Heparin in moderate to high concentration (10 to 100 U/mL) exhibited concentration-related inhibition of FCS- and PDGF-BB-stimulated SMC migration; however, a low concentration (1 U/mL) of heparin had no inhibitory effects. Heparin also had weak inhibitory effects on nonstimulated SMC migration. The SMCs that were exposed to a high concentration (100 U/mL) of heparin for 6 hours were capable of migrating after a short lag period of removal of heparin from the culture medium. These SMCs also showed recovery of responses to FCS and PDGF-BB by migrating significantly greater than the nonstimulated level. Furthermore, heparin-containing medium did not contain detached cells. These results indicate that heparin inhibits human coronary artery SMC migration, especially when stimulated by FCS or PDGF-BB, and that this inhibitory effect of heparin is reversible and not simply a function of killing cells.
肝素作为一种抗凝剂，在实验研究中已显示可减少血管损伤后的新生内膜增殖和再狭窄，但肝素在冠状动脉球囊血管成形术中的临床试验结果却为阴性。因此，本研究采用博伊登小室法，检测了肝素对培养的人冠状动脉平滑肌细胞（SMC）在基础状态下或由血清及血小板衍生生长因子（PDGF）-BB刺激后的迁移作用。此外，还检测了肝素对人冠状动脉SMC迁移作用的可逆性。胎牛血清（FCS）和PDGF-BB以浓度依赖的方式刺激SMC迁移。中至高浓度（10至100 U/mL）的肝素对FCS和PDGF-BB刺激的SMC迁移呈现出浓度相关的抑制作用；然而，低浓度（1 U/mL）的肝素则无抑制作用。肝素对未受刺激的SMC迁移也有微弱的抑制作用。在培养基中去除肝素后的短暂延迟期后，暴露于高浓度（100 U/mL）肝素6小时的SMC仍能够迁移。这些SMC对FCS和PDGF-BB的反应也恢复了，其迁移显著大于未受刺激的水平。此外，含肝素的培养基中没有脱落的细胞。这些结果表明，肝素可抑制人冠状动脉SMC迁移，尤其是在受到FCS或PDGF-BB刺激时，并且肝素的这种抑制作用是可逆的，并非仅仅是杀死细胞的作用。
