Investigation of the role of von Willebrand factor in shear-induced platelet activation and functional alteration under high non-physiological shear stress.
Investigation of the role of von Willebrand factor in shear-induced platelet activation and functional alteration under high non-physiological shear stress.
复制标题
研究冯维勒布兰德因子在高非生理剪切应力下剪切诱导的血小板活化和功能改变中的作用。
DOI：
10.1111/aor.14698
复制
发表时间：
2024
影响因子：
2.4
通讯作者：
Wu,ZhongjunJ
中科院分区：
文献类型：
--
作者：
Han,Dong;Sun,Wenji;Clark,KierstenP;Griffith,BartleyP;Wu,ZhongjunJ
Backgroundvon Willebrand factor (vWF) plays a crucial role in physiological hemostasis through platelet and subendothelial collagen adhesion. However, its role in shear‐induced platelet activation and functional alteration under non‐physiological conditions common to blood‐contacting medical devices (BCMDs) is not well investigated.MethodsFresh healthy human blood was treated with an anti‐vWF antibody to block vWF–GPIbα interaction. Untreated blood was used as a control. They were exposed to three levels of non‐physiological shear stress (NPSS) (75, 125, and 175 Pa) through a shearing device with an exposure time of 0.5 s to mimic typical shear conditions in BCMDs. Flow cytometric assays were used to measure the expression levels of PAC‐1 and P‐Selectin and platelet aggregates for platelet activation and the expression levels of GPIbα, GPIIb/IIIa, and GPVI for receptor shedding. Collagen/ristocetin‐induced platelet aggregation capacity was characterized by aggregometry.ResultsThe levels of platelet activation and aggregates increased with increasing NPSS in the untreated blood. More receptors were lost with increasing NPSS, resulting in a decreased capacity of collagen/ristocetin‐induced platelet aggregation. In contrast, the increase in platelet activation and aggregates after exposure to NPSS, even at the highest level of NPSS, was significantly lower in treated blood. Nevertheless, there was no notable difference in receptor shedding, especially for GPIIb/IIIa and GPVI, between the two blood groups at the same level of NPSS. The block of vWF exacerbated the decreased capacity of collagen/ristocetin‐induced platelet aggregation.ConclusionsHigh NPSS activates platelets mainly by enhancing the vWF–GPIbα interaction. Platelet activation and receptor shedding induced by high NPSS likely occur through different pathways.
