Coronavirus disease 2019 (COVID-19) includes the cardiovascular complications in addition to respiratory disease. SARS-CoV-2 infection impairs endothelial function and induces vascular inflammation, leading to endotheliitis. SARS-CoV-2 infection relies on the binding of Spike glycoprotein (S protein) to angiotensin converting enzyme 2 (ACE2) in the host cells. We show here that S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial function, decreased ACE2 expression and eNOS activity, and increased glycolysis. The underlying mechanism involves S protein downregulation of AMPK and upregulation of MDM2, causing ACE2 destabilization. Thus, the S protein-exerted vascular endothelial damage via ACE2 downregulation overrides the decreased virus infectivity.

中文翻译：

---

SARS-CoV-2 Spike蛋白通过下调ACE2损害内皮功能。

2019年冠状病毒病（COVID-19）除呼吸系统疾病外还包括心血管并发症。SARS-CoV-2感染会损害内皮功能并引起血管炎症，从而导致内皮炎。SARS-CoV-2感染依赖于宿主细胞中钉状糖蛋白（S蛋白）与血管紧张素转化酶2（ACE2）的结合。我们在这里显示，单独的S蛋白可以在体外和体内破坏血管内皮细胞（ECs），表现为线粒体功能受损，ACE2表达和eNOS活性降低以及糖酵解增加。潜在的机制涉及AMPK的S蛋白下调和MDM2的上调，从而引起ACE2不稳定。因此，通过ACE2的下调，S蛋白对血管内皮的损害覆盖了降低的病毒感染性。