Endothelial Dysfunction, Inflammation, and Oxidative Stress in COVID-19—Mechanisms and Therapeutic Targets

Abstract

The outbreak of the COVID-19 pandemic represents an ongoing healthcare emergency responsible for more than 3.4 million deaths worldwide. COVID-19 is the disease caused by SARS-CoV-2, a virus that targets not only the lungs but also the cardiovascular system. COVID-19 can manifest with a wide range of clinical manifestations, from mild symptoms to severe forms of the disease, characterized by respiratory failure due to severe alveolar damage. Several studies investigated the underlying mechanisms of the severe lung damage associated with SARS-CoV-2 infection and revealed that the respiratory failure associated with COVID-19 is the consequence not only of acute respiratory distress syndrome but also of macro- and microvascular involvement. New observations show that COVID-19 is an endothelial disease, and the consequent endotheliopathy is responsible for inflammation, cytokine storm, oxidative stress, and coagulopathy. In this review, we show the central role of endothelial dysfunction, inflammation, and oxidative stress in the COVID-19 pathogenesis and present the therapeutic targets deriving from this endotheliopathy.

Intermedin Reduces Oxidative Stress and Apoptosis in Ventilator-Induced Lung Injury via JAK2/STAT3

“…Excessive oxidative stress generated by injured ECs is widely involved in the progression of lung damage during VILI ( Fodor et al, 2021 ). The imbalance of ROS is the main driving factor for oxidative stress ( Piera-Velazquez and Jimenez, 2021 ).…”

“…In HPMECs, ROS was measured by detecting the fluorescence intensity of DCF, and we found that IMD significantly alleviated the generation of ROS induced by VILI ( Figure 3B ). SOD and MDA are important indices for evaluating the antioxidant and oxidative capacities of oxidative stress ( Fodor et al, 2021 ). In vivo and in vitro , compared with the VILI group, IMD pretreatment significantly increased SOD levels and decreased MDA levels ( Figures 3C,D ).…”

“…ECs are widely distributed throughout the body and have a large surface area. They mainly regulate the body’s homeostasis through six functions: regulating vasodilation-contraction, vascular permeability, cell growth, immunity and inflammation, coagulation function, cell growth, and lipid metabolism ( Daiber et al, 2017 ; Fodor et al, 2021 ). Because the ability of endothelial cells to resist external stimulation is weak, endothelial cells are the firs to be affected and changed in acute lung injury ( Wiener-Kronish et al, 1991 ; Matthay et al, 2019 ).…”

“…However, excessive degradation or inactivation of NO caused by the increase in ROS is one of the main reasons for the decrease in NO bioavailability ( Lind et al, 2017 ; Yepuri and Ramasamy, 2019 ). Upon injury, the production of ROS may be excessive, and the balance between oxidative stress and antioxidant stress is broken, EC function is destroyed, and apoptosis increases, which has a negative impact on cell and tissue function ( Kuzkaya et al, 2003 ; Landmesser et al, 2003 ; Fodor et al, 2021 ). Therefore, it is essential to detect the oxidative and antioxidant stress functions of ECs in VILI.…”

COVID-19–Associated Endothelial Dysfunction and Microvascular Injury

“…Endothelial dysfunction may result from a combination of direct viral effects, as suggested by the presence of viral elements within the endothelium in autopsies from patients who died of COVID19, and a consequence of virus dependent activation of inflammatory response ( 27 ). Moreover, endothelial changes are multiorgan, indicating that endothelial dysfunction may be involved in numerous symptoms of SARS-CoV-2-positive patients ( 28 ). Injury of endothelial cells is involved in several pathophysiological mechanisms which may promote the occurrence of micro and macrovascular involvement in COVID19 infection.…”