Mori Daisuke, Yano Koichiro, Tsubota Ken-ichi, Ishikawa Takuji, Wada Shigeo, Yamaguchi Takami
Department of Bioengineering and Robotics, Tohoku University, 6-6-01 Aoba, Aoba-ku, Sendai, Miyagi 980-8579, Japan.
Thromb Res. 2008;123(1):114-21. doi: 10.1016/j.thromres.2008.03.006. Epub 2008 May 2.
The primary thrombus formation is a critical phenomenon both physiologically and pathologically. It has been seen that various mechanical factors are involved the regulation of primary thrombus formation through a series of physiological and biochemical processes, including blood flow and intercellular molecular bridges. However, it has not been fully understood how the existence of red blood cells contributes to the process of platelet thrombus formation. We computationally analyzed the motions of platelets in plasma layer above which red blood cells flow assuming a background simple shear flow of a shear rate of 1000 s(-1) using Stokesian dynamics. In the computation, fluid mechanical interactions between platelets and red blood cells were taken into account together with the binding forces via plasma proteins between two platelets and between a platelet and injured vessel wall. The process of the platelets aggregation was significantly dependent on whether red blood cells were present. When red blood cells were absent, the aggregate formed grew more vertically compared to the case with red blood cells. Conversely, when red blood cells were present, the aggregate spread more horizontally because the red blood cells constrained the vertical growth when the height of the aggregate reached the level of the red blood cells. Our results suggest that red blood cells mechanically play a significant role in primary thrombus formation, which accelerates the horizontal spread of the thrombus, and point out the necessity of considering the presence of red blood cells when investigating the mechanism of thrombus formation.
原发性血栓形成在生理和病理方面都是一个关键现象。业已发现,各种机械因素通过一系列生理和生化过程参与原发性血栓形成的调节,这些过程包括血流和细胞间分子桥。然而,红细胞的存在如何促进血小板血栓形成过程尚未完全明确。我们采用斯托克斯动力学方法,在假设剪切速率为1000 s(-1)的背景简单剪切流条件下,对红细胞在其上方流动的血浆层中血小板的运动进行了计算分析。在计算中,考虑了血小板与红细胞之间的流体力学相互作用,以及两个血小板之间和血小板与受损血管壁之间通过血浆蛋白产生的结合力。血小板聚集过程显著依赖于红细胞是否存在。当不存在红细胞时,与存在红细胞的情况相比,形成的聚集体在垂直方向上生长得更多。相反,当存在红细胞时,聚集体在水平方向上扩展得更多,因为当聚集体高度达到红细胞水平时,红细胞会限制其垂直生长。我们的结果表明,红细胞在原发性血栓形成过程中在力学方面发挥着重要作用,它加速了血栓的水平扩展,并指出在研究血栓形成机制时考虑红细胞存在的必要性。