Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, the Netherlands (J.W.M.H.).
Faculty of Medicine and Centre for Hybrid Biodevices, University of Southampton, United Kingdom (J.W.).
Arterioscler Thromb Vasc Biol. 2022 May;42(5):540-552. doi: 10.1161/ATVBAHA.121.317092. Epub 2022 Mar 17.
This review discusses our understanding of platelet diversity with implications for the roles of platelets in hemostasis and thrombosis and identifies advanced technologies set to provide new insights. We use the term diversity to capture intrasubject platelet variability that can be intrinsic or governed by the environment and lead to a heterogeneous response pattern of aggregation, clot promotion, and external communication. Using choice examples, we discuss how the use of advanced technologies can provide new insights into the underlying causes of platelet molecular, structural, and functional diversity. As sources of diversity, we discuss the proliferating megakaryocytes with different allele-specific expression patterns, the asymmetrical formation of proplatelets, changes in platelets induced by aging and priming, interplatelet heterogeneity in thrombus organization and stability, and platelet-dependent communications. We provide indications how current knowledge gaps can be addressed using promising technologies, such as next-generation sequencing, proteomic approaches, advanced imaging techniques, multicolor flow and mass cytometry, multifunctional microfluidics assays, and organ-on-a-chip platforms. We then argue how this technology base can aid in characterizing platelet populations and in identifying platelet biomarkers relevant for the treatment of cardiovascular disease.
这篇综述讨论了我们对血小板多样性的理解，其对血小板在止血和血栓形成中的作用具有重要意义，并确定了有望提供新见解的先进技术。我们使用“多样性”一词来描述个体内血小板的可变性，这种可变性可以是内在的，也可以受环境影响，并导致聚集、促进血栓形成和外部通讯的异质反应模式。我们通过选择示例讨论了如何使用先进技术深入了解血小板分子、结构和功能多样性的根本原因。作为多样性的来源，我们讨论了具有不同等位基因特异性表达模式的增殖巨核细胞、不匀称的前血小板形成、衰老和诱导引起的血小板变化、血栓组织和稳定性中的血小板间异质性，以及血小板依赖性通讯。我们提供了如何使用有前途的技术（如下一代测序、蛋白质组学方法、先进的成像技术、多色流式和质谱细胞术、多功能微流控分析和芯片上器官平台）解决当前知识空白的指示。然后，我们论证了这种技术基础如何有助于表征血小板群体，并确定与心血管疾病治疗相关的血小板生物标志物。
