Zilberman-Rudenko Jevgenia, Itakura Asako, Maddala Jeevan, Baker-Groberg Sandra M, Vetter Ralf, Tucker Erik I, Gruber András, Gerdes Christoph, McCarty Owen J T
Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA.
Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA; Drug Discovery, Bayer Pharma AG, Wuppertal, Germany.
Cell Mol Bioeng. 2016 Dec;9(4):496-508. doi: 10.1007/s12195-016-0448-5. Epub 2016 May 26.
Thrombus growth at the site of vascular injury is mediated by the sequential events of platelet recruitment, activation and aggregation concomitant with the initiation of the coagulation cascade, resulting in local thrombin generation and fibrin formation. While the biorheology of a localized thrombus formation has been well studied, it is unclear whether local sites of thrombin generation propagate platelet activation within the bloodstream. In order to study the physical biology of platelet activation downstream of sites of thrombus formation, we developed a platform to measure platelet activation and microaggregate formation in the bloodstream. Our results show that thrombi formed on collagen and tissue factor promote activation and aggregation of platelets in the bloodstream in a convection-dependent manner. Pharmacological inhibition of the coagulation factors (F) X, XI or thrombin dramatically reduced the degree of distal platelet activation and microaggregate formation in the bloodstream without affecting the degree of local platelet deposition and aggregation on a surface of immobilized collagen. Herein we describe the development and an example of the utility of a platform to study platelet activation and microaggregate formation in the bloodstream (convection-limited regime) relative to the local site of thrombus formation.
血管损伤部位的血栓形成是由血小板募集、激活和聚集的一系列事件介导的，同时伴随着凝血级联反应的启动，导致局部凝血酶生成和纤维蛋白形成。虽然局部血栓形成的生物流变学已经得到了充分研究，但尚不清楚凝血酶生成的局部部位是否会在血流中传播血小板激活。为了研究血栓形成部位下游血小板激活的物理生物学，我们开发了一个平台来测量血流中的血小板激活和微聚集体形成。我们的结果表明，在胶原蛋白和组织因子上形成的血栓以对流依赖的方式促进血流中血小板的激活和聚集。对凝血因子X、XI或凝血酶的药理抑制显著降低了血流中远端血小板激活和微聚集体形成的程度，而不影响固定化胶原蛋白表面局部血小板沉积和聚集的程度。在此，我们描述了一个平台的开发及其应用实例，该平台用于研究相对于血栓形成局部部位的血流中（对流受限状态）血小板激活和微聚集体形成。
