Department of Medicine, Division of Pulmonary and Critical Care, University of California, Los Angeles, California, United States.
Cardiovascular Research Institute, Department of Medicine and Anesthesia, University of California, San Francisco, California, United States.
Am J Physiol Lung Cell Mol Physiol. 2023 Apr 1;324(4):L393-L399. doi: 10.1152/ajplung.00353.2022. Epub 2023 Feb 7.
Acute respiratory distress syndrome (ARDS) has had no mortality-improving pharmacological intervention despite 50 years of high-caliber research due to its heterogeneity (Huppert LA, Matthay MA, Ware LB. 40: 31-39, 2019). For the field to advance, better definitions for ARDS subgroups that more uniformly respond to therapies are needed (Bos LDJ, Scicluna BP, Ong DSY, Cremer O, van der Poll T, Schultz MJ. 200: 42-50, 2019; Dickson RP, Schultz MJ, T van der P, Schouten LR, Falkowski NR, Luth JE, Sjoding MW, Brown CA, Chanderraj R, Huffnagle GB, Bos LDJ, Biomarker Analysis in Septic ICU Patients (BASIC) Consortium. 201: 555-563, 2020; Sinha P, Calfee CS. 200: 4-6, 2019; Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, NHLBI ARDS Network. 2: 611-620, 2014; Hendrickson CM, Matthay MA. 8: 1-12, 2018). A plethora of high-quality clinical research has uncovered the next generation of soluble biomarkers that provide the predictive enrichment necessary for trial recruitment; however, plasma-soluble markers do not specify the damaged organ of origin nor do they provide insight into disease mechanisms. In this perspective, we make the case for querying the transcriptome of circulating endothelial cells (CECs), which when shed from vessels after inflammatory insult, become heralds of site-specific inflammatory damage. We review the application of CEC quantification to multiple disease phenotypes (including myocardial infarction, vasculitides, cancer, and ARDS), in each case supporting the association of CEC number with disease severity. We also argue for the utility of single-cell RNA transcriptomics to the understanding of cell-specific contributions to disease pathophysiology and its potential to uncover novel insight on signals contributing to CEC shedding in ARDS.
急性呼吸窘迫综合征（ARDS）尽管经过 50 年的高质量研究，但由于其异质性，仍没有改善死亡率的药物干预措施（Huppert LA、Matthay MA、Ware LB. 40: 31-39, 2019）。为了推动该领域的发展，需要更好地定义对治疗更均匀响应的 ARDS 亚组（Bos LDJ、Scicluna BP、Ong DSY、Cremer O、van der Poll T、Schultz MJ. 200: 42-50, 2019；Dickson RP、Schultz MJ、T van der P、Schouten LR、Falkowski NR、Luth JE、Sjoding MW、Brown CA、Chanderraj R、Huffnagle GB、Bos LDJ、Biomarker Analysis in Septic ICU Patients (BASIC) Consortium. 201: 555-563, 2020；Sinha P、Calfee CS. 200: 4-6, 2019；Calfee CS、Delucchi K、Parsons PE、Thompson BT、Ware LB、Matthay MA、NHLBI ARDS Network. 2: 611-620, 2014；Hendrickson CM、Matthay MA. 8: 1-12, 2018）。大量高质量的临床研究揭示了下一代可溶性生物标志物，为试验招募提供了必要的预测性富集；然而，血浆可溶性标志物既不能确定受损的起源器官，也不能提供对疾病机制的深入了解。在这篇观点文章中，我们提出了一个案例，即查询循环内皮细胞（CEC）的转录组，当血管受到炎症损伤后，CEC 从血管中脱落，成为特定部位炎症损伤的先兆。我们回顾了 CEC 定量在多种疾病表型（包括心肌梗死、血管炎、癌症和 ARDS）中的应用，在每种情况下，CEC 数量与疾病严重程度相关。我们还认为，单细胞 RNA 转录组学有助于理解细胞特异性对疾病病理生理学的贡献，并有可能揭示 ARDS 中导致 CEC 脱落的信号的新见解。
