Katz Ben-Zion, Muhl Lars, Zwang Etty, Ilan Neta, Herishanu Yair, Deutsch Varda, Naparstek Elizabeth, Vlodavsky Israel, Preissner Klaus T
The Hematology Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239, Israel.
Thromb Haemost. 2007 Dec;98(6):1193-9.
A key element for the physiological restriction of blood coagulation at the endothelial cell surface is its non-thrombogenic property, mainly attributed to cell surface heparan sulfate proteoglycans. Heparanase is an endo-beta-D-glucuronidase with specific heparan sulfate degrading activity, which is produced and stored in platelets, and is released upon their activation. We examined the effects of heparanase pro-enzyme on coagulation functions, predominantly under physiological conditions. While heparanase pro-enzyme does not directly affect coagulation protein activities, it has profound effects on heparinoid-mediated regulation of coagulation responses, apparently via mechanisms that do not involve its enzymatic activity. Heparanase pro-enzyme reverses the anti-coagulant activity of unfractionated heparin on the coagulation pathway as well as on thrombin activity. In addition, heparanase pro-enzyme abrogated the factor X inhibitory activity of low-molecular-weight heparin (LMWH). The pro-coagulant effects of the non-active heparanase were also exerted by its major functional heparin-binding peptide. Finally, the effects of heparanase on the activity of factor VII activating protease that is auto-activated by heparinoids indicated a complete antagonistic action of heparanase in this system. Altogether, heparanase pro-coagulant activities that were also demonstrated in plasma samples from patients under LMWH treatment, point to a possible use of this molecule as antagonist for heparinoid treatment.
内皮细胞表面对血液凝固进行生理限制的一个关键因素是其非血栓形成特性，这主要归因于细胞表面的硫酸乙酰肝素蛋白聚糖。乙酰肝素酶是一种具有特定硫酸乙酰肝素降解活性的内切-β-D-葡糖醛酸酶，它在血小板中产生并储存，并在血小板激活时释放。我们主要在生理条件下研究了乙酰肝素酶原对凝血功能的影响。虽然乙酰肝素酶原不直接影响凝血蛋白活性，但它对类肝素介导的凝血反应调节有深远影响，显然是通过不涉及其酶活性的机制。乙酰肝素酶原可逆转普通肝素对凝血途径以及凝血酶活性的抗凝活性。此外，乙酰肝素酶原消除了低分子量肝素（LMWH）的因子X抑制活性。无活性的乙酰肝素酶的促凝作用也由其主要的功能性肝素结合肽发挥。最后，乙酰肝素酶对由类肝素自动激活的因子VII激活蛋白酶活性的影响表明，在该系统中乙酰肝素酶具有完全的拮抗作用。总之，在接受LMWH治疗的患者血浆样本中也证实了乙酰肝素酶的促凝活性，这表明该分子可能用作类肝素治疗的拮抗剂。
