Introduction

We have experienced a pandemic induced by the interaction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) structural proteins with innate structures. These interactions are especially prevalent for patients with underlying pathologies, such as cardiovascular diseases. However, there has been limited work to uncover the range of responses induced by SARS-CoV-2 structural proteins. Thus, our objective was to investigate how endothelial cell pro-thrombotic and pro-inflammatory responses are altered after exposure to SARS-CoV-2 spike, nucleocapsid, and membrane-envelope proteins. We hypothesized that after a short duration exposure, endothelial cells would have a heightened thrombotic and inflammatory potential. With longer exposures, this may lead to altered disease progression and the observed increased mortality and morbidity rates in patients with underlying vascular pathologies.

Methods

To test this hypothesis, human endothelial cells were exposed to SARS-CoV-2 structural proteins. After the exposure, the expression of thrombomodulin, PECAM-1, connexin-43, and gC1qR were assessed. In parallel, standard cell culture readouts were assessed to determine if these incubations altered cell growth and metabolism.

Results and Conclusions

We observed significant increases in thrombotic and inflammatory marker expression, with no change to the cell culture parameters (with the exception of a reduction in cell density in response to one SARS-CoV-2 structural protein). Importantly, these observations were dependent on the viral structural protein the cells were exposed to, suggesting that the interactions of SARS-CoV-2 with innate cells is complex and must be uncovered. Combined, this suggests that SARS-CoV-2 structural proteins can regulate inflammatory and thrombotic responses that underlie common pathologies observed during COVID-19.

中文翻译：

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SARS-CoV-2 结构蛋白暴露会改变人类内皮细胞的血栓和炎症反应

介绍

我们经历了由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 结构蛋白与先天结构相互作用引起的大流行。这些相互作用对于患有潜在疾病（例如心血管疾病）的患者尤其普遍。然而，揭示 SARS-CoV-2 结构蛋白诱导的反应范围的工作有限。因此，我们的目标是研究在暴露于 SARS-CoV-2 刺突蛋白、核衣壳蛋白和膜包膜蛋白后，内皮细胞促血栓形成和促炎反应如何改变。我们假设在短时间暴露后，内皮细胞将具有更高的血栓形成和炎症潜能。有了更长的曝光时间，

方法

为了验证这一假设，人类内皮细胞暴露于 SARS-CoV-2 结构蛋白。暴露后，评估血栓调节蛋白、PECAM-1、连接蛋白43和gC1qR的表达。同时，评估标准细胞培养读数以确定这些培养是否改变了细胞生长和新陈代谢。

结果和结论

我们观察到血栓形成和炎症标志物表达显着增加，而细胞培养参数没有变化（除了响应一种 SARS-CoV-2 结构蛋白导致细胞密度降低）。重要的是，这些观察结果取决于细胞接触的病毒结构蛋白，这表明 SARS-CoV-2 与先天细胞的相互作用是复杂的，必须加以揭示。综合起来，这表明 SARS-CoV-2 结构蛋白可以调节炎症和血栓形成反应，这些反应是 COVID-19 期间观察到的常见病理的基础。