Thrombosis and Hemostasis Unit, Department of Hematology, Rambam Health Care Campus, Haifa, Israel.
Thromb Res. 2012 Apr;129 Suppl 1:S76-9. doi: 10.1016/S0049-3848(12)70021-X.
Heparanase that was cloned from and is abundant in the placenta is implicated in cell invasion, tumor metastasis and angiogenesis. We have recently demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. Heparanase was shown to up-regulate tissue factor (TF) expression and interact with tissue factor pathway inhibitor (TFPI) on cell surface, leading to dissociation of TFPI from cell membrane of endothelial and tumor cells, resulting in increased cell surface coagulation activity. We have lately shown that heparanase directly enhances TF activity resulting in increased factor Xa production and activation of the coagulation system. Data indicate increased plasma levels of heparanase suggesting its possible involvement in pregnancy vascular complications. Elevation in heparanase levels and procoagulant activity was also documented in orthopedic surgery patients receiving prophylactic doses of enoxaparin. Taking into account the pro-metastatic and pro-angiogenic functions of heparanase, with over-expression in human malignancies and abundance in platelets and placenta, its involvement in the coagulation machinery is an intriguing novel platform for further research.
从胎盘大量克隆的肝素酶与细胞浸润、肿瘤转移和血管生成有关。我们最近的研究表明，肝素酶可能还以非酶的方式影响止血系统。肝素酶被证明可上调组织因子（TF）的表达，并与细胞表面的组织因子途径抑制剂（TFPI）相互作用，导致 TFPI 从内皮细胞和肿瘤细胞膜上解离，从而增加细胞表面的凝血活性。我们最近发现肝素酶直接增强 TF 的活性，导致因子 Xa 的产生增加和凝血系统的激活。数据表明，肝素酶的血浆水平升高提示其可能参与妊娠血管并发症。接受依诺肝素预防性剂量的骨科手术患者的肝素酶水平和促凝活性也升高。考虑到肝素酶的促转移和促血管生成功能，在人类恶性肿瘤中过度表达，以及在血小板和胎盘中丰富，其在凝血机制中的参与是进一步研究的一个有趣的新平台。
