Graduate Program in Medicine - Pathological Anatomy, Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Brain's Biomedicine Lab, Paulo Niemeyer State Brain Institute, Rio de Janeiro, Brazil.
Brain's Biomedicine Lab, Paulo Niemeyer State Brain Institute, Rio de Janeiro, Brazil.
Vascul Pharmacol. 2021 Apr;137:106829. doi: 10.1016/j.vph.2021.106829. Epub 2021 Jan 8.
Angiotensin-converting enzyme 2 (ACE2) is an important player of the renin-angiotensin-aldosterone system (RAAS) in regulating the conversion of angiotensin II into angiotensin (1-7). While expressed on the surface of human cells, such as lung, heart, kidney, neurons, and endothelial cells (EC), ACE2 is the entry receptor for SARS-CoV-2. Here, we would like to highlight that ACE2 is predominant on the EC membrane. Many of coronavirus disease 2019 (COVID-19) symptoms have been associated with the large recruitment of immune cells, directly affecting EC. Additionally, cytokines, hypoxia, and complement activation can trigger the activation of EC leading to the coagulation cascade. The EC dysfunction plus the inflammation due to SARS-CoV-2 infection may lead to abnormal coagulation, actively participating in thrombo-inflammatory processes resulting in vasculopathy and indicating poor prognosis in patients with COVID-19. Considering the intrinsic relationship between EC and the pathophysiology of SARS-CoV-2, EC-associated therapies such as anticoagulants, fibrinolytic drugs, immunomodulators, and molecular therapies have been proposed. In this review, we will discuss the role of EC in the lung inflammation and edema, in the disseminate coagulation process, ACE2 positive cancer patients, and current and future EC-associated therapies to treat COVID-19.
血管紧张素转换酶 2（ACE2）是肾素-血管紧张素-醛固酮系统（RAAS）中调节血管紧张素 II 转化为血管紧张素（1-7）的重要因子。虽然 ACE2 表达于人类细胞表面，如肺、心脏、肾脏、神经元和内皮细胞（EC），但它是 SARS-CoV-2 的进入受体。在这里，我们想强调的是 ACE2 主要存在于 EC 膜上。许多 2019 冠状病毒病（COVID-19）症状与大量免疫细胞的募集直接影响 EC 有关。此外，细胞因子、缺氧和补体激活可触发 EC 的激活，导致凝血级联反应。由于 SARS-CoV-2 感染导致的 EC 功能障碍和炎症可能导致异常凝血，积极参与血栓炎症过程，导致血管病变，并预示着 COVID-19 患者的预后不良。鉴于 EC 与 SARS-CoV-2 病理生理学之间的内在关系，已经提出了针对 EC 的治疗方法，如抗凝剂、纤维蛋白溶解药物、免疫调节剂和分子疗法。在这篇综述中，我们将讨论 EC 在肺炎症和水肿、弥散性凝血过程、ACE2 阳性癌症患者中的作用，以及目前和未来针对 COVID-19 的 EC 相关治疗方法。
