The rapid change of shear rate gradient is beneficial to platelet activation

作者全名："Zhang, Tiancong; Liu, Ling; Huang, Xiaojing; Gao, Xuemei; Huan, Xuanrong; He, Cui; Li, Yuan"

作者地址："[Zhang, Tiancong; Huang, Xiaojing; Gao, Xuemei; Huan, Xuanrong; He, Cui; Li, Yuan] Chongqing Med Univ, Yong Chuan Hosp, Cent Lab, Chongqing, Peoples R China; [Zhang, Tiancong] Sichuan Univ, West China Hosp, Dept Lab Med, Chengdu, Sichuan, Peoples R China; [Liu, Ling] Sichuan Univ, West China Hosp, Dept Ophthalmol, Chengdu, Sichuan, Peoples R China; [Li, Yuan] Chongqing Med Univ, Yongchuan Hosp, Cent Lab, Chongqing 402160, Peoples R China"

通信作者："Li, Y (通讯作者)，Chongqing Med Univ, Yongchuan Hosp, Cent Lab, Chongqing 402160, Peoples R China."

来源：PLATELETS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001125271500001

JCR分区：Q2

影响因子：2.5

年份：2024

卷号：35

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Cardiovascular disease; microfluidic chip; PI3K/AKT signal pathway; platelet reactivity; shear gradient change rate; von Willebrand factor activity

摘要："Fluid shear plays a key role in hemostasis and thrombosis, and the purpose of this study was to investigate the effect of shear gradient change rate (SGCR) on platelet reactivity and von Willebrand factor (vWF) activity and its mechanism. In this study, we developed a set of microfluidic chips capable of generating different shear gradients and simulated the shear rate distribution in the flow field by COMSOL Multiphysics software. Molecular markers of platelet activation (P-selectin, activated GPIIb/IIIa, phosphatidylserine exposure, and monocyte-platelet aggregate formation) were analyzed by flow cytometry. Platelet aggregation induced by shear gradient was studied by a microfluidic experimental platform, and plasma vWF ristocetin cofactor (vWF: RCO) activity was investigated by flow cytometry. The expression of p-Akt was studied by Western blotting. The results showed that the faster the SGCR, the higher the expression of platelet p-Akt, and the stronger the platelet reactivity and vWF activity. This indicates that fluid shear stress can activate platelets and vWF in a shear gradient-dependent manner through the PI3K/AKT signal pathway, and the faster the SGCR, the more significant the activation effect. What is the context?Recent studies have shown that fluid shear stress plays a key role in platelet activation and thrombosis. However, its mechanism and effect have not been fully elucidated.The development of microfluidic chip technology enables people to study platelet function in a precisely controlled flow field environment.Previous studies have shown that the PI3K-AKT signal pathway may be a mechanically sensitive signal transduction pathway.What is new?In this study, we designed a microfluidic model with different narrow geometry, and controlled the injection pump to perfuse fluid at the same flow rate, so that the platelets flowing through the model experienced the flow field environment of different shear gradients.We studied the activities of platelets and von Willebrand factor in different flow fields and explored their signal transduction pathways.What is the impact?Our results suggest that vascular stenosis does increase platelet activity and the risk of thrombosis. However, its ability to activate platelets is not only related to the peak shear rate and shear time, but also closely related to the decreasing rate of shear gradient. Even if the peak shear rate at the stenosis is the same, the faster the shear rate decreases, the higher the reactivity of platelets and von Willebrand factor, which may be mediated by the PI3K-AKT signal pathway. This study not only helps clinicians to judge the risk of thrombosis in patients with atherosclerosis or percutaneous coronary intervention, but also helps us to better understand the mechanism of shear-induced platelet activation."

基金机构：National Natural Sciences Foundation of China [11702047]; Special Project of Science and Technology Innovation for People's Livelihood Security of Chongqing [cstc2017shmsA130009]; Chongqing Medical Research Program [2017MSXM079]; Postdoctoral Research Project of Chongqing [Xm2017082]

基金资助正文："This work was supported by the National Natural Sciences Foundation of China [11702047], the Special Project of Science and Technology Innovation for People's Livelihood Security of Chongqing [cstc2017shmsA130009], the Chongqing Medical Research Program [2017MSXM079], and the Postdoctoral Research Project of Chongqing [Xm2017082]."