Lung protection in severe COVID-19 by means of Tie2 agonism (C06)

通过 Tie2 激动剂 (C06) 保护重症 COVID-19 中的肺部

• 批准号: 178727205
• 金额: --
• 依托单位: UGMLC-Professur für Molecular Pneumology
• 依托单位国家: 德国
• 项目类别: CRC/Transregios
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/178727205?language=en
• 关键词: Lung; protection; severe; COVID; 19

COVID-19 causes failure of the alveolo-capillary barrier, a characteristic for life-threatening ARDS. The Ang/Tie2 pathway was shown to be centrally involved in the regulation of lung barrier function in pneumonia. Therefore, we will specifically (1) quantify Ang-2 levels in serum of hospitalised COVID-19 patients and analyse its prognostic/predictive value regarding COVID-19 trajectories and outcome, as compared to CAP of other origin; (2) evaluate the protective effect of Tie2 agonism on endothelial permeability in vitro induced by serum of COVID-19 patients, and (3) study different barrier stabilizing interventions targeting Tie2 signaling in hamster models of SARS-CoV-2 infection. The data collected in these experiments are expected to establish the Ang/Tie2 system as a critical regulator of lung barrier integrity in COVID-19, and will provide a rationale for risk stratification in COVID-19 and treatment of COVID-19 associated ARDS based on the Ang/Tie2 system.

COVID-19 会导致肺泡毛细血管屏障衰竭，这是危及生命的 ARDS 的一个特征。 Ang/Tie2 通路被证明主要参与肺炎肺屏障功能的调节。因此，我们将具体 (1) 量化住院 COVID-19 患者血清中的 Ang-2 水平，并与其他来源的 CAP 相比，分析其对 COVID-19 轨迹和结果的预后/预测价值； (2) 评估 Tie2 激动剂对 COVID-19 患者血清诱导的体外内皮通透性的保护作用，以及 (3) 在 SARS-CoV-2 感染的仓鼠模型中研究针对 Tie2 信号传导的不同屏障稳定干预措施。这些实验中收集的数据预计将确立 Ang/Tie2 系统作为 COVID-19 肺屏障完整性的关键调节剂，并将为 COVID-19 风险分层和基于 Ang/Tie2 系统治疗 COVID-19 相关 ARDS 提供理论依据。