European heart journal, 2020-09-01, Vol.41 (32), p.3038-3044
The vascular endothelium provides the crucial interface between the blood compartment and tissues, and displays a series of remarkable properties that normally maintain homeostasis. This tightly regulated palette of functions includes control of haemostasis, fibrinolysis, vasomotion, inflammation, oxidative stress, vascular permeability, and structure. While these functions participate in the moment-to-moment regulation of the circulation and coordinate many host defence mechanisms, they can also contribute to disease when their usually homeostatic and defensive functions over-reach and turn against the host. SARS-CoV-2, the aetiological agent of COVID-19, causes the current pandemic. It produces protean manifestations ranging from head to toe, wreaking seemingly indiscriminate havoc on multiple organ systems including the lungs, heart, brain, kidney, and vasculature. This essay explores the hypothesis that COVID-19, particularly in the later complicated stages, represents an endothelial disease. Cytokines, protein pro-inflammatory mediators, serve as key danger signals that shift endothelial functions from the homeostatic into the defensive mode. The endgame of COVID-19 usually involves a cytokine storm, a phlogistic phenomenon fed by well-understood positive feedback loops that govern cytokine production and overwhelm counter-regulatory mechanisms. The concept of COVID-19 as an endothelial disease provides a unifying pathophysiological picture of this raging infection, and also provides a framework for a rational treatment strategy at a time when we possess an indeed modest evidence base to guide our therapeutic attempts to confront this novel pandemic.
Thrombosis - physiopathology ; Pandemics ; Cytokines - metabolism ; Oxidative Stress ; Humans ; Endothelium, Vascular - physiopathology ; COVID-19 ; SARS-CoV-2 ; Thrombosis - metabolism ; Coronavirus Infections - epidemiology ; Pneumonia, Viral - epidemiology ; Thrombosis - etiology ; Pneumonia, Viral - complications ; Betacoronavirus ; Coronavirus Infections - complications ; Index Medicus ; Viewpoint ; Cytokine ; MED00200 ; Inflammation ; Microvasculature ; AcademicSubjects ; Thrombosis ; Endothelium
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