Endothelial cells and SARS-CoV-2: An intimate relationship

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.

Automated summary

ACE2 plays a crucial role in regulating the renin-angiotensin-aldosterone system (RAAS) and acts as an entry receptor for SARS-CoV-2 on endothelial cells. The dysfunction of endothelial cells, triggered by factors such as cytokines, hypoxia, and complement activation, may lead to abnormal coagulation and inflammation, contributing to poor prognosis in COVID-19 patients. Endothelial cell-associated therapies, including anticoagulants and immunomodulators, have been proposed to treat COVID-19.