Quantifying Platelet Margination in Diabetic Blood Flow
Quantifying Platelet Margination in Diabetic Blood Flow
复制标题
DOI：
10.1016/j.bpj.2018.08.031
复制
发表时间：
2018-10-02
影响因子：
3.4
通讯作者：
Karniadakis, George Em
中科院分区：
文献类型：
--
作者：
Chang, Hung-Yu;Yazdani, Alireza;Karniadakis, George Em
2型糖尿病（T2DM）患者发生与心血管疾病密切相关的血栓形成异常。除了许多凝血因子的变化，如凝血酶和纤维蛋白原水平升高，血液中流动的红细胞（RBC）和血小板的异常流变学效应在T2DM的血小板粘附和血栓形成中至关重要。导致后者的一个重要过程是血小板边缘化。我们采用耗散粒子动力学方法无缝建模细胞，血浆和血管壁。我们通过考虑健康和T2DM血液中不同的细胞形状、大小和RBC变形性，以及可变的流速和红细胞压积，对圆柱形血管中的RBC和血小板运输进行了系统研究。特别是，我们使用细胞水平的RBC和血小板模型，参数来自患者特定的数据，并提出了一个敏感性研究。我们发现，与正常RBC相比，T2DM RBC的变形性较小，血小板向血管壁的转运降低，而平均体积较高的血小板（通常在T2DM中观察到）导致边缘化增强。此外，增加流速或红细胞压积增强血小板边集。我们还研究了血小板形状的影响，并观察到一个非单调的变化与最高的近壁浓度对应的血小板具有适度的纵横比为0.38。我们研究了白色血细胞（WBC）的作用，其计数在2型糖尿病患者中显著增加。我们发现，白细胞滚动或白细胞粘附倾向于减少血小板边缘由于流体动力学效应。据我们所知，以前从未对包括所有血细胞在内的血液进行过此类模拟，我们的定量研究结果有助于将流体动力学相互作用的影响与粘附相互作用分开，并可能阐明T2DM中的相关病理过程，如炎症反应增加、血小板活化和粘附以及最终血栓形成。
Patients with type 2 diabetes mellitus (T2DM) develop thrombotic abnormalities strongly associated with cardiovascular diseases. In addition to the changes of numerous coagulation factors such as elevated levels of thrombin and fibrinogen, the abnormal rheological effects of red blood cells (RBCs) and platelets flowing in blood are crucial in platelet adhesion and thrombus formation in T2DM. An important process contributing to the latter is the platelet margination. We employ the dissipative particle dynamics method to seamlessly model cells, plasma, and vessel walls. We perform a systematic study on RBC and platelet transport in cylindrical vessels by considering different cell shapes, sizes, and RBC deformabilities in healthy and T2DM blood, as well as variable flowrates and hematocrit. In particular, we use cellular-level RBC and platelet models with parameters derived from patient-specific data and present a sensitivity study. We find T2DM RBCs, which are less deformable compared to normal RBCs, lower the transport of platelets toward the vessel walls, whereas platelets with higher mean volume (often observed in T2DM) lead to enhanced margination. Furthermore, increasing the flowrate or hematocrit enhances platelet margination. We also investigated the effect of platelet shape and observed a nonmonotonic variation with the highest near-wall concentration corresponding to platelets with a moderate aspect ratio of 0.38. We examine the role of white blood cells (WBCs), whose count is increased notably in T2DM patients. We find that WBC rolling or WBC adhesion tends to decrease platelet margination due to hydrodynamic effects. To the best of our knowledge, such simulations of blood including all blood cells have not been performed before, and our quantitative findings can help separate the effects of hydrodynamic interactions from adhesive interactions and potentially shed light on the associated pathological processes in T2DM such as increased inflammatory response, platelet activation and adhesion, and ultimately thrombus formation.