Abstract：
BACKGROUND: Endothelial dysfunction plays a central role in the pathophysiology of COVID-19 and is closely linked to the severity and mortality of the disease. The inflammatory response to SARS-CoV-2 infection can alter the capacity of the endothelium to regulate vascular tone, immune responses, and the balance between anti-thrombotic and pro-thrombotic properties. However, the specific endothelial pathways altered during COVID-19 still need to be fully understood.
OBJECTIVE: In this study, we sought to identify molecular changes in endothelial cells induced by circulating factors characteristic of COVID-19.
RESULTS: To this aim, we cultured endothelial cells with sera from patients with COVID-19 or non-COVID-19 pneumonia. Through transcriptomic analysis, we were able to identify a distinctive endothelial phenotype that is induced by sera from COVID-19 patients. We confirmed and expanded this observation in vitro by showing that COVID-19 serum alters functional properties of endothelial cells leading to increased apoptosis, loss of barrier integrity, and hypercoagulability. Furthermore, we demonstrated that these endothelial dysfunctions are mediated by protease-activated receptor 2 (PAR-2), as predicted by transcriptome network analysis validated by in vitro functional assays.
CONCLUSIONS: Our findings provide the rationale for further studies to evaluate whether targeting PAR-2 may be a clinically effective strategy to counteract endothelial dysfunction in COVID-19.
OBJECTIVE: In this study, we sought to identify molecular changes in endothelial cells induced by circulating factors characteristic of COVID-19.
RESULTS: To this aim, we cultured endothelial cells with sera from patients with COVID-19 or non-COVID-19 pneumonia. Through transcriptomic analysis, we were able to identify a distinctive endothelial phenotype that is induced by sera from COVID-19 patients. We confirmed and expanded this observation in vitro by showing that COVID-19 serum alters functional properties of endothelial cells leading to increased apoptosis, loss of barrier integrity, and hypercoagulability. Furthermore, we demonstrated that these endothelial dysfunctions are mediated by protease-activated receptor 2 (PAR-2), as predicted by transcriptome network analysis validated by in vitro functional assays.
CONCLUSIONS: Our findings provide the rationale for further studies to evaluate whether targeting PAR-2 may be a clinically effective strategy to counteract endothelial dysfunction in COVID-19.
摘要：
背景：内皮功能障碍在COVID-19的病理生理学中起着重要作用，并且与疾病的严重程度和死亡率密切相关。SARS-CoV-2感染的炎症反应可以改变内皮调节血管张力的能力，免疫反应，以及抗血栓形成和促血栓形成特性之间的平衡。然而,COVID-19过程中特定的内皮通路改变仍需要充分了解。
目的：在本研究中，我们试图鉴定COVID-19特有的循环因子诱导的内皮细胞分子变化.
结果：为此，我们用COVID-19或非COVID-19肺炎患者的血清培养内皮细胞。通过转录组学分析，我们能够从COVID-19患者中鉴定出一种由血清诱导的独特内皮表型.我们在体外证实并扩大了这一观察结果，表明COVID-19血清改变了内皮细胞的功能特性，导致细胞凋亡增加，屏障完整性的丧失，和高凝状态。此外，我们证明了这些内皮功能障碍是由蛋白酶激活受体2（PAR-2）介导的，正如转录组网络分析预测的那样，通过体外功能测定验证。
结论：我们的发现为进一步研究提供了依据，以评估靶向PAR-2是否可能是对抗COVID-19内皮功能障碍的临床有效策略。
目的：在本研究中，我们试图鉴定COVID-19特有的循环因子诱导的内皮细胞分子变化.
结果：为此，我们用COVID-19或非COVID-19肺炎患者的血清培养内皮细胞。通过转录组学分析，我们能够从COVID-19患者中鉴定出一种由血清诱导的独特内皮表型.我们在体外证实并扩大了这一观察结果，表明COVID-19血清改变了内皮细胞的功能特性，导致细胞凋亡增加，屏障完整性的丧失，和高凝状态。此外，我们证明了这些内皮功能障碍是由蛋白酶激活受体2（PAR-2）介导的，正如转录组网络分析预测的那样，通过体外功能测定验证。
结论：我们的发现为进一步研究提供了依据，以评估靶向PAR-2是否可能是对抗COVID-19内皮功能障碍的临床有效策略。
