血管生成素样蛋白4是新冠病毒疾病严重程度的新型标志物。
Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity.
作者信息
Bhatraju Pavan K, Morrell Eric D, Stanaway Ian B, Sathe Neha A, Srivastava Avantika, Postelnicu Radu, Green Richard, Andrews Adair, Gonzalez Martin, Kratochvil Christopher J, Kumar Vishakha K, Hsiang Tien-Ying, Gale Michael, Anesi George L, Wyles David, Broadhurst M Jana, Brett-Major David, Mukherjee Vikramjit, Sevransky Jonathan E, Landsittel Douglas, Hung Chi, Altemeier William A, Gharib Sina A, Uyeki Timothy M, Cobb J Perren, Liebler Janice M, Crosslin David R, Jarvik Gail P, Segal Leopoldo N, Evans Laura, Mikacenic Carmen, Wurfel Mark M
机构信息
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington Medical Center, Seattle, WA.
School of Medicine, University of Washington, Sepsis Center of Research Excellence-University of Washington (SCORE-UW), Seattle, WA.
出版信息
Crit Care Explor. 2022 Dec 30;5(1):e0827. doi: 10.1097/CCE.0000000000000827. eCollection 2023 Jan.
UNLABELLED
Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak.
OBJECTIVES
To assess the role of ANGPTL4 in COVID-19-related outcomes.
DESIGN SETTING AND PARTICIPANTS
Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University.
MAIN OUTCOMES AND MEASURES
Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4.
RESULTS
Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log increase, 1.53; 95% CI, 1.17-2.00; = 0.002). Higher ANGPTL4 concentrations were also associated with higher proportions of venous thromboembolism and acute respiratory distress syndrome. Longitudinal ANGPTL4 concentrations were significantly different during the first 2 weeks of hospitalization in patients who subsequently died compared with survivors ( for interaction = 8.1 × 10). Proteomics analysis demonstrated abundance of ANGPTL4 in lung tissue compared with other organs in COVID-19. single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls.
CONCLUSIONS AND RELEVANCE
ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients.
未标注
血管功能障碍和毛细血管渗漏在重症COVID-19患者中很常见，但对参与COVID-19发病机制的内皮途径的识别有限。血管生成素样4（ANGPTL4）是一种在缺氧和营养缺乏条件下分泌的蛋白质，具有多种生物学效应，包括血管损伤和毛细血管渗漏。
目的
评估ANGPTL4在COVID-19相关结局中的作用。
设计、设置和参与者：2020年4月至2021年5月，从华盛顿大学、南加州大学和纽约大学三个不同医疗中心进行的一项前瞻性、多中心队列研究中，招募了225名COVID-19重症监护病房患者。
主要结局和测量指标
在重症监护病房入院后第1、7和14天测量血浆ANGPTL4。我们使用先前发表的组织蛋白质组学数据和从COVID-19患者收集的标本的肺单核RNA（snRNA）测序数据，以确定产生ANGPTL4的组织和细胞。
结果
较高的血浆ANGPTL4浓度与较差的医院死亡率显著相关（每对数增加的调整优势比，1.53；95%可信区间，1.17 - 2.00；P = 0.002）。较高的ANGPTL4浓度也与静脉血栓栓塞和急性呼吸窘迫综合征的较高比例相关。与幸存者相比，随后死亡的患者在住院的前2周内纵向ANGPTL4浓度有显著差异（交互作用P = 8.1×10）。蛋白质组学分析表明，与COVID-19中的其他器官相比，肺组织中ANGPTL4含量丰富。与对照组相比，COVID-19肺组织中肺泡2型上皮细胞和成纤维细胞中的单核RNA基因表达显著增加。
结论及相关性
ANGPTL4在肺上皮细胞和成纤维细胞中表达，并与重症COVID-19患者的临床预后相关。
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