Impact of rise and fall phases of shear on platelet activation and aggregation using microfluidics

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

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

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

来源：JOURNAL OF THROMBOSIS AND THROMBOLYSIS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001194796700001

JCR分区：Q2

影响因子：2.3

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Shear rise and fall phase; Von willebrand factor; Microfluidics; Platelet; Thrombosis

摘要："Blood flow disorders are often the result of the non-physiological narrowing of blood arteries caused by atherosclerosis and thrombus. The blood then proceeds through rising-peak-decreasing phases as it passes through the narrow area. Although abnormally high shear is known to activate platelets, the shear process that platelets undergo in small arteries is complex. Thus, understanding how each shear phase affects platelet activation can be used to improve antiplatelet therapy and decrease the risk of side effects like bleeding. Blood samples were sheared (68.8 ms,5200 s-1) in vitro by the microfluidic technique, and platelet activation levels (P-selectin and integrin alpha IIb beta 3) and von Willebrand factor (vWF) binding to platelets were analyzed by flow cytometry. Post-stenosis platelet aggregation was dynamically detected using microfluidic technology. We studied TXA2, P2Y12-ADP, and integrin alpha IIb beta 3-fibrinogen receptor pathways by adding antiplatelet drugs, such as acetylsalicylic acid (ASA, an active ingredient of aspirin that inhibits platelet metabolism), ticagrelor (hinders platelet activation), and tirofiban (blocks integrin alpha IIb beta 3 receptor) in vitro, respectively, to determine platelet activation function mediated by transient non-physiological high shear rates. We demonstrated that platelets can be activated under transient pathological high shear rates. The shear rise and fall phases influenced shear-induced platelet activation by regulating the binding of vWF to platelets. The degree of platelet activation and aggregation increased with multiple shear rise and fall phases. ASA did not inhibit shear-mediated platelet activation, but ticagrelor and tirofiban effectively inhibited shear-mediated platelet activation. Our data demonstrated that the shear rise and fall phases play an important role in shear-mediated platelet activation and promote platelet activation and aggregation in a vWF-dependent manner. Blocking integrin alpha IIb beta 3 receptor and hindering P2Y12-ADP were beneficial to reducing shear-mediated platelet activation."

基金机构：National Natural Science Foundation of China

基金资助正文：No Statement Available