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

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Abstract

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 αIIbβ3) 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 αIIbβ3-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 αIIbβ3 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 αIIbβ3 receptor and hindering P2Y12-ADP were beneficial to reducing shear-mediated platelet activation.

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Funding

National Natural Science Foundation of China (11702047); Joint project of Chongqing Health Commission and Science and Technology Bureau (2023GDRC008); Graduate Innovation Fund of Yongchuan Hospital affiliated to Chongqing Medical University (YJSCX202204).

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Authors and Affiliations

  1. Central Laboratory of Yong-Chuan Hospital, Chongqing Medical University, Chongqing, China

    Xuemei Gao, Xiaojing Huang & Yuan Li

  2. Department of Laboratory, West China Hospital, Sichuan University, Sichuan, China

    Tiancong Zhang

  3. Department of Clinical Laboratory of Yong-Chuan Hospital, Chongqing Medical University, Chongqing, China

    Xuanrong Huan

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  1. Xuemei Gao
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Contributions

Xuemei Gao contributed to the study design, data collection, statistical analysis, data interpretation, and manuscript preparation. Tiancong Zhang contributed to data collection. Xiaojing Huang contributed to statistical analysis, and Xuanrong Huan contributed to data collection and statistical analysis. Yuan Li contributed to the manuscript preparation. All authors read and approved the final manuscript.

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Correspondence to Yuan Li.

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Gao, X., Zhang, T., Huang, X. et al. Impact of rise and fall phases of shear on platelet activation and aggregation using microfluidics. J Thromb Thrombolysis 57, 576–586 (2024). https://doi.org/10.1007/s11239-024-02968-1

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