Effect of pathological high shear exposure time on platelet activation and aggregation

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

作者地址："[Zhang, Tiancong; Huang, Xiaojing; Gao, Xuemei; Liu, Ling; Chen, Dan; Huan, Xuanrong; Li, Yuan] Chongqing Med Univ, Cent Lab Yong Chuan Hosp, Chongqing, Peoples R China; [He, Cui] Chongqing Med Univ, Dept Blood Transfus Yong Chuan Hosp, Chongqing, Peoples R China"

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

来源：CLINICAL HEMORHEOLOGY AND MICROCIRCULATION

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001035843300002

JCR分区：Q3

影响因子：2.1

年份：2023

卷号：84

期号：2

开始页：125

结束页：139

文献类型：Article

关键词：Pathological high shear; platelet activation and aggregation; microfluidics

摘要："Circulating platelets are sometimes exposed to high shear rate environments due to vascular stenosis, and the effect of transiently elevated pathological high shear rates on platelet activation and aggregation function has not been clarified. The aim of this study was to investigate the effect of pathological high shear rate (8302s(-1)) exposure time (3.16-25.3 ms) on platelet activation and aggregation function. In addition, by adding active ingredients of antiplatelet drugs such as ASA (an active ingredient of aspirin), Ticagrelor, Tirofiban and GP1BA (platelet membrane protein GPIb inhibitor) in vitro, we studied TXA(2), P2Y(12)-ADP, GPIIb/IIIa-fibrinogen and GPIb /IX/V-vWF receptor pathways to determine platelet activation function mediated by pathological high shear rate. In this study, we designed a set of microfluidic chips with stenosis lengths of 0.5 mm, 1 mm, 2 mm, 3 mm, and 4 mm, all with 80% stenosis, to generate pathological high shear forces that can act at different times. The whole blood flowing through the microchannels was collected by perfusion of sodium citrate anticoagulated whole blood at a physiological arterial shear rate (1500 s(-1)), and the expression levels of platelet surface activation markers (P-selectin and GP IIb/IIIa) and the degree of platelet aggregation were analyzed by flow cytometry; platelet aggregation patterns were observed by microscopic examination of blood smears. The results showed that shearing significantly increased platelet activation and aggregation levels compared to un-sheared whole blood, and the activation and aggregation levels increased with increasing duration of pathological high shear rate. In vitro inhibition studies showed that ASA barely inhibited the expression of P-selectin and PAC-1 on the platelet surface; Ticagrelor effectively inhibited the expression of both P-selectin and PAC-1; Tirofiban significantly inhibited the expression of PAC-1 on the platelet surface and slightly inhibited the expression of P-selectin; GP1BA significantly inhibited the expression of both. Our results suggest that transient pathological high shear rate (8302s(-1)) exposure can induce platelet activation in a time-dependent manner; however, the mechanism is more complex and may be due to the following reasons: transient elevated pathological high shear rate activates platelets through the GPIb/IX/V-vWF receptor pathway, and after platelet activation, its surface membrane protein GPIIb/IIIa receptors activate platelets through fibrinogen to form platelet-platelet aggregates, and further activation of active substances such as ADP and TXA(2) released by platelet alpha particles, which contribute to the formation of irreversible platelet aggregation."

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 scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau) [2023GDRC008]; 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), Special Project of Science and Technology Innovation for People's Livelihood Security of Chongqing (cstc2017shmsA130009), the Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau (2023GDRC008), and the Postdoctoral Research Project of Chongqing (Xm2017082)."