Miesbach Wolfgang
Department of Haemostaseology and Haemophilia Center, Institute of Transfusion Medicine, Medical Clinic 2, University Hospital Frankfurt, Frankfurt, Germany.
TH Open. 2020 Jun 26;4(2):e138-e144. doi: 10.1055/s-0040-1713678. eCollection 2020 Apr.
The activated renin-angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin-angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1-7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin-angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1-7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.
激活的肾素-血管紧张素系统会导致凝血与纤溶失衡，从而引发血栓前状态。血管紧张素II是激活的肾素-血管紧张素系统的核心效应分子，可被血管紧张素转换酶2降解为血管紧张素（1-7）。新型冠状病毒感染（归类为COVID-19）由新型冠状病毒SARS-CoV-2引起，其特征是炎症反应过度，在一部分患者（大多为有基础合并症的老年患者）中可导致严重表现，如急性呼吸窘迫综合征、脓毒症和死亡。SARS-CoV-2利用血管紧张素转换酶2受体进入靶细胞，从而激活肾素-血管紧张素系统。血管紧张素转换酶2下调后，血管收缩剂血管紧张素II生成增加，而其拮抗调节分子血管紧张素（1-7）减少。血管紧张素II会增加凝血酶的形成并损害纤溶功能。在重症COVID-19患者中，其水平升高与病毒载量及肺损伤密切相关。因此，COVID-19严重并发症患者的复杂临床表现是由高表达的血管紧张素II对血管病变、凝血病和炎症的多种作用引发的。未来的治疗选择应侧重于阻断COVID-19患者血管紧张素II的促血栓形成和炎症特性。
