Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been led to a pandemic emergency. So far, different pathological pathways for SARS-CoV-2 infection have been introduced in which the excess release of pro-inflammatory cytokines (such as interleukin 1 β [IL-1β], IL-6, and tumor necrosis factor α [TNFα]) has earned most of the attentions. However, recent studies have identified new pathways with at least the same level of importance as cytokine storm in which endothelial cell (EC) dysfunction is one of them. In COVID-19, two main pathologic phenomena have been seen as a result of EC dysfunction: hyper-coagulation state and pathologic angiogenesis. The EC dysfunction-induced hypercoagulation state seems to be caused by alteration in the levels of different factors such as plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF) antigen, soluble thrombomodulin, and tissue factor pathway inhibitor (TFPI). As data have shown, these thromboembolic events are associated with severity of disease severity or even death in COVID-19 patients. Other than thromboembolic events, pathologic angiogenesis is among the recent findings. Furthermore, over-expression/higher levels of different proangiogenic factors such as vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1 α (HIF-1α), IL-6, TNF receptor super family 1A and 12, and angiotensin-converting enzyme 2 (ACE2) have been found in the lung biopsies/sera of both survived and non-survived COVID-19 patients. Also, there are some hypotheses regarding the role of nitric oxide in EC dysfunction and acute respiratory distress syndrome (ARDS) in SARS-CoV-2 infection. It has been demonstrated that different pathways involved in inflammation are generally common with EC dysfunction and angiogenesis. Altogether, considering the common possible upstream pathways in cytokine storm, pathologic angiogenesis, and EC dysfunction, it seems that targeting these molecules (such as nuclear factor κB) could be more effective in the management of patients with COVID-19. Graphical abstract Unlabelled Image
【저자키워드】 Inflammation, Coronavirus disease 2019, Cytokine storm, Angiogenesis, ACE2, angiotensin-converting enzyme 2, Coagulation, endothelial cells, NO, Nitric Oxide, VEGF, Vascular endothelial growth factor, PRRs, Pattern Recognition Receptors, TNF-α, tumor necrosis factor α, PAI-1, plasminogen activator inhibitor-1, AT, antithrombin, ADP, adenosine diphosphate, ATP, adenosine triphosphate, COX-2, cyclooxygenase-2, PAMPs, pathogen-associated molecular patterns, NF-κB, nuclear factor κB, NOS, nitric oxide synthase, IL-1β, interleukin 1β, IL-6, interleukin 6, EC, endothelial cell, VCAM-1, Vascular cell adhesion molecule-1,