Omics of endothelial cell dysfunction in sepsis.
Omics of endothelial cell dysfunction in sepsis.
复制标题
DOI：
10.1530/vb-22-0003
复制
发表时间：
2022-02-01
期刊：
影响因子：
--
通讯作者：
Kiani, Mohammad F
中科院分区：
文献类型：
--
作者：
Langston, Jordan C;Rossi, Michael T;Yang, Qingliang;Ohley, William;Perez, Edwin;Kilpatrick, Laurie E;Prabhakarpandian, Balabhaskar;Kiani, Mohammad F
在脓毒症期间，定义为由于宿主对感染的反应失调而导致的危及生命的器官功能障碍，全身性炎症激活内皮细胞并启动多方面的促炎信号传导事件级联，导致渗透性增加和白细胞过度募集。血管内皮细胞具有许多共同的特性，但具有器官特异性表型，具有独特的结构和功能。因此，需要针对内皮细胞表型的疗法来解决器官特异性内皮细胞功能障碍。组学允许研究生物系统中表达的基因、蛋白质和/或代谢物，并提供关于正常和疾病条件下信号的时间和空间演变的见解。蛋白质组学定量蛋白质表达，识别蛋白质-蛋白质相互作用，并可以揭示内皮细胞中的机械变化，这些变化不可能通过单独的还原方法进行研究。在这篇综述中，我们提供了一个概述，脓毒症的病理生理学如何影响组学的重点是蛋白质组学分析的小鼠内皮细胞在脓毒症/炎症及其与临床相关的人类内皮细胞组学的关系。我们讨论了组学如何被用来定义脓毒症的内型签名在不同的人群中，专注于在器官特异性微血管内皮细胞在脓毒症或脓毒症样炎症的蛋白质组学分析。我们认为，研究定义脓毒症的内皮细胞表型的蛋白质组表达的基础上，迫切需要补充全血组学分析和更好地定义脓毒症的亚表型。最后，我们提供了一个讨论，如何在计算机建模可以用来利用大量的组学数据来映射脓毒症的反应途径。
During sepsis, defined as life-threatening organ dysfunction due to dysregulated host response to infection, systemic inflammation activates endothelial cells and initiates a multifaceted cascade of pro-inflammatory signaling events, resulting in increased permeability and excessive recruitment of leukocytes. Vascular endothelial cells share many common properties but have organ-specific phenotypes with unique structure and function. Thus, therapies directed against endothelial cell phenotypes are needed to address organ-specific endothelial cell dysfunction. Omics allow for the study of expressed genes, proteins and/or metabolites in biological systems and provide insight on temporal and spatial evolution of signals during normal and diseased conditions. Proteomics quantifies protein expression, identifies protein–protein interactions and can reveal mechanistic changes in endothelial cells that would not be possible to study via reductionist methods alone. In this review, we provide an overview of how sepsis pathophysiology impacts omics with a focus on proteomic analysis of mouse endothelial cells during sepsis/inflammation and its relationship with the more clinically relevant omics of human endothelial cells. We discuss how omics has been used to define septic endotype signatures in different populations with a focus on proteomic analysis in organ-specific microvascular endothelial cells during sepsis or septic-like inflammation. We believe that studies defining septic endotypes based on proteomic expression in endothelial cell phenotypes are urgently needed to complement omic profiling of whole blood and better define sepsis subphenotypes. Lastly, we provide a discussion of how in silico modeling can be used to leverage the large volume of omics data to map response pathways in sepsis.