Platelet Proteomes, Pathways, and Phenotypes as Informants of Vascular Wellness and Disease.
Platelet Proteomes, Pathways, and Phenotypes as Informants of Vascular Wellness and Disease.
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DOI：
10.1161/atvbaha.120.314647
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Aslan JE
中科院分区：
文献类型：
--
作者：
Aslan JE
血小板在形式和功能上迅速发生反应性转变，以修复血管内皮并介导止血。相反，具有一系列引发或难治表型的异质性血小板亚群在慢性炎症和其他病症中以可能指示或支持疾病的方式逐渐出现。可区分的血小板表型越来越多地与各种生理和病理情况相关;然而，血小板表型变异的起源和意义仍然不清楚，概念模糊。由于疾病中血小板功能的变化与血小板激动剂受体激活后的血小板表现出许多相似性，因此血小板对止血和炎症的细胞内反应可能为血小板表型的分子基础提供见解。在这里，我们回顾了蛋白质水平关系的概念-从血小板受体到细胞内信号传导事件-可能有助于定义炎症，免疫反应，衰老和其他条件下的血小板表型。我们进一步讨论了如何代表系统范围内的血小板蛋白质组学数据配置文件的因果关系相关的细胞内事件，或，通路图，电路样网络，可能会通知血小板表型的分子定义。除了提供对血小板作为药物靶点的见解外，血小板功能的因果排列细胞内关系图还可以通过利用血小板作为血管健康和疾病的可访问的、动态的、内源性的循环生物标志物来推进精确和拦截医学工作。
Platelets rapidly undergo responsive transitions in form and function to repair vascular endothelium and mediate hemostasis. In contrast, heterogeneous platelet subpopulations with a range of primed or refractory phenotypes gradually arise in chronic inflammatory and other conditions in a manner that may indicate or support disease. Qualitatively distinguishable platelet phenotypes are increasingly associated with a variety of physiological and pathological circumstances; however, the origins and significance of platelet phenotypic variation remain unclear and conceptually vague. As changes in platelet function in disease exhibit many similarities to platelets following the activation of platelet agonist receptors, the intracellular responses of platelets common to hemostasis and inflammation may provide insights to the molecular basis of platelet phenotype. Here, we review concepts around how protein-level relations – from platelet receptors through intracellular signaling events – may help to define platelet phenotypes in inflammation, immune responses, aging and other conditions. We further discuss how representing systems-wide platelet proteomics data profiles as circuit-like networks of causally related intracellular events, or, pathway maps, may inform molecular definitions of platelet phenotype. In addition to offering insights into platelets as druggable targets, maps of causally arranged intracellular relations underlying platelet function can also advance precision and interceptive medicine efforts by leveraging platelets as accessible, dynamic, endogenous, circulating biomarkers of vascular wellness and disease.