ADP and Thromboxane Inhibitors Both Reduce Global Contraction of Clot Length, While Thromboxane Inhibition Attenuates Internal Aggregate Contraction

K. Trigani, Michael Decortin, S. Diamond
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引用次数: 1

Abstract

Platelet contractility drives clot contraction to enhance clot density and stability. Clot contraction is typically studied under static conditions, with fewer studies of wall-adherent platelet clots formed under flow. We tested the effect of inhibitors of ADP and/or thromboxane A2 (TXA2) signaling on clot contraction. Using an eight-channel microfluidic device, we perfused PPACK-treated whole blood (WB) ± acetylsalicylic acid (ASA), 2-methylthioAMP (2-MeSAMP), and/or MRS-2179 over collagen (100/s) for 7.5 min, then stopped flow to observe contraction for 7.5 minutes. Two automated imaging methods scored fluorescent platelet percent contraction over the no-flow observation period: (1) “global” measurement of clot length and (2) “local” changes in surface area coverage of the numerous platelet aggregates within the clot. Total platelet fluorescence intensity (FI) decreased with concomitant decrease in global aggregate contraction when ASA, 2-MeSAMP, and/or MRS-2179 were present. Total platelet FI and global aggregate contraction were highly correlated ( R 2  = 0.87). In contrast, local aggregate contraction was more pronounced than global aggregate contraction across all inhibition conditions. However, ASA significantly reduced local aggregate contraction relative to conditions without TXA2 inhibition. P-selectin display was significantly reduced by ADP and TXA2 inhibition, but there was limited detection of global or local aggregate contraction in P-selectin-positive platelets across all conditions, as expected for densely packed “core” platelets. Our results demonstrate that global aggregate contraction is inhibited by ASA, 2-MeSAMP, and MRS-2179, while ASA more potently inhibited local aggregate contraction. These results help resolve how different platelet antagonists affect global and local clot structure and function.
ADP和血栓素抑制剂均可减少血栓长度的整体收缩,而血栓素抑制剂可减弱内部聚集收缩
血小板收缩驱动凝块收缩,增强凝块密度和稳定性。凝块收缩通常在静态条件下进行研究,较少研究在流动条件下形成的壁贴血小板凝块。我们测试了ADP和/或血栓素A2 (TXA2)信号抑制剂对血栓收缩的影响。采用八通道微流控装置,将ppack处理过的全血(WB)±乙酰水杨酸(ASA)、2-甲基硫代amp (2-MeSAMP)和/或MRS-2179灌注于胶原蛋白(100/s)上7.5 min,然后停流观察收缩7.5 min。两种自动化成像方法在无血流观察期间对荧光血小板收缩百分比进行评分:(1)“全局”测量血块长度;(2)血块内众多血小板聚集体表面积覆盖范围的“局部”变化。当ASA、2-MeSAMP和/或MRS-2179存在时,血小板总荧光强度(FI)下降,同时整体聚集性收缩减少。血小板总FI与血小板总收缩高度相关(r2 = 0.87)。相比之下,在所有抑制条件下,局部骨料收缩比全局骨料收缩更为明显。然而,相对于没有TXA2抑制的情况,ASA显著减少了局部聚集体收缩。ADP和TXA2抑制显著降低了p -选择素的显示,但在所有条件下,p -选择素阳性血小板中检测到的整体或局部聚集性收缩有限,正如预期的密集排列的“核心”血小板。我们的研究结果表明,ASA、2-MeSAMP和MRS-2179抑制了整体聚集体收缩,而ASA更有效地抑制了局部聚集体收缩。这些结果有助于解决不同的血小板拮抗剂如何影响整体和局部凝块结构和功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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