Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA.
Biology Department, Augustana University, Sioux Falls, SD 57197, USA.
Int J Mol Sci. 2024 Nov 8;25(22):11990. doi: 10.3390/ijms252211990.
Platelet activation plays an essential role in clot formation to prevent blood loss following vascular damage. In pathologic conditions, platelet activation can lead to obstructive clots, disrupting blood flow and resulting in thrombosis. Native Americans suffer disproportionately from arterial disease and previous research has shown that Blacks are enriched in genetic polymorphisms that correlate with higher platelet reactivity contributing to an increased risk for thrombosis. Therefore, the current study sought to determine phenotypic variations in Native American platelet responses following stimulation with agonists, simulating vascular damage. Several donors from a small cohort of Native Americans showed atypical robust platelet aggregation when stimulated with submaximal concentrations of agonists. Further, when comparing α-granule secretion, a specific marker of platelet activation, Native Americans were more likely to have elevated responses to multiple agonist conditions of stimulation compared to Whites. Interestingly, there were no noticeable differences in integrin activation between Native Americans and Whites. Our study is the first to observe elevated Native American platelet responses compared to Whites, supporting further mechanistic studies and investigation of treatment approaches for the prevention of thrombosis.
血小板活化在血管损伤后防止出血的血栓形成中起着至关重要的作用。在病理条件下，血小板活化可导致阻塞性血栓形成，破坏血流并导致血栓形成。美洲原住民不成比例地患有动脉疾病，先前的研究表明，黑人富含与更高的血小板反应性相关的遗传多态性，这增加了血栓形成的风险。因此，目前的研究旨在确定在模拟血管损伤的激动剂刺激下，美洲原住民血小板反应的表型变化。来自一小部分美洲原住民的几个供体在接受低浓度激动剂刺激时表现出异常强烈的血小板聚集。此外，当比较血小板活化的特定标志物α-颗粒分泌时，与白人相比，美洲原住民对多种激动剂刺激条件的反应更有可能升高。有趣的是，在整合素活化方面，美洲原住民和白人之间没有明显差异。我们的研究是首次观察到与白人相比，美洲原住民血小板反应升高，支持进一步的机制研究和血栓预防治疗方法的探索。
