Platelets. 2012;23(5):409-12. doi: 10.3109/09537104.2011.625509. Epub 2011 Oct 19.
Homocysteine (Hcys) and homocysteine thiolactone (HTL) concentrations in organism are correlated with a number of serious pathologies. In the literature, there are few papers describing studies on the effects of homocysteine on proteins that participate in blood coagulation and fibrinolysis in human. However, mechanisms involved in the relationship between hyperhomocysteinemia and hemostatic process are still unclear. The role of N- or S-homocysteinylation (induced by Hcys and its derivatives) of different hemostatic proteins, including fibrinogen is also still poorly known. The aim of this study was to establish the functional changes of the fibrinogen molecule induced by Hcys (at final doses of 10-100 µM) and the most reactive form of Hcys - its cyclic thioester, homocysteine thiolactone (0.1-1 µM), and to examine the effects of these changes on the capability of fibrinogen to interact with human blood platelets (by measuring the platelet adhesion). Our present results demonstrated that Hcys-treated fibrinogen in comparison with native molecule had a distinct capability to mediate platelet adhesion. Both, unstimulated and thrombin-activated platelets showed a reduced ability to adhere to Hcys-mediated fibrinogen. HTL (at all tested concentrations) had similar properties when we used thrombin-activated platelets. In conclusion, the results reported in this study could be useful for a better understanding of changes in hemostasis during hyperhomocysteinemia.
同型半胱氨酸（Hcys）和同型半胱氨酸硫内酯（HTL）在体内的浓度与许多严重的病理有关。在文献中，很少有描述同型半胱氨酸对参与人体凝血和纤溶的蛋白质的影响的研究。然而，高同型半胱氨酸血症与止血过程之间关系的机制仍不清楚。N-或 S-同型半胱氨酸化（由 Hcys 及其衍生物诱导）对包括纤维蛋白原在内的不同止血蛋白的作用也知之甚少。本研究的目的是确定 Hcys（终末剂量为 10-100µM）和最具反应性的 Hcys 形式 - 同型半胱氨酸硫内酯（0.1-1µM）诱导的纤维蛋白原分子的功能变化，并研究这些变化对纤维蛋白原与人类血小板相互作用能力的影响（通过测量血小板黏附）。我们目前的结果表明，与天然分子相比，Hcys 处理的纤维蛋白原具有明显介导血小板黏附的能力。未刺激和凝血酶激活的血小板对 Hcys 介导的纤维蛋白原的黏附能力均降低。在使用凝血酶激活的血小板时，HTL（在所有测试浓度下）具有相似的性质。总之，本研究报告的结果可能有助于更好地理解高同型半胱氨酸血症期间止血的变化。
