Endothelial Dysfunction through Oxidatively Generated Epigenetic Mark in Respiratory Viral Infections

Abstract

The bronchial vascular endothelial network plays important roles in pulmonary pathology during respiratory viral infections, including respiratory syncytial virus (RSV), influenza A(H1N1) and importantly SARS-Cov-2. All of these infections can be severe and even lethal in patients with underlying risk factors.A major obstacle in disease prevention is the lack of appropriate efficacious vaccine(s) due to continuous changes in the encoding capacity of the viral genome, exuberant responsiveness of the host immune system and lack of effective antiviral drugs. Current management of these severe respiratory viral infections is limited to supportive clinical care. The primary cause of morbidity and mortality is respiratory failure, partially due to endothelial pulmonary complications, including edema. The latter is induced by the loss of alveolar epithelium integrity and by pathological changes in the endothelial vascular network that regulates blood flow, blood fluidity, exchange of fluids, electrolytes, various macromolecules and responses to signals triggered by oxygenation, and controls trafficking of leukocyte immune cells. This overview outlines the latest understanding of the implications of pulmonary vascular endothelium involvement in respiratory distress syndrome secondary to viral infections. In addition, the roles of infection-induced cytokines, growth factors, and epigenetic reprogramming in endothelial permeability, as well as emerging treatment options to decrease disease burden, are discussed.

COVID-19 and Pulmonary Angiogenesis: The Possible Role of Hypoxia and Hyperinflammation in the Overexpression of Proteins Involved in Alveolar Vascular Dysfunction

“…The study also found that H1N1pdm09 infection can lead to milder endothelial dysfunction. These findings suggest that COVID-19 can lead to severe vascular compromise, with the presence of microthrombi and the marked expression of inflammatory mediators [ 7 ].…”

“…However, the results of this study support the idea that both Influenza A and SARS-CoV-2 increase macrophage activation and chemokines expression. IL-6 has been established as a reliable marker for the severity and mortality of COVID-19 in clinical practice, and its antagonist has been shown to reduce mortality in hospitalized COVID-19 patients [ 5 , 7 , 9 , 16 , 17 , 18 , 19 ].…”

“…Our work found that a large proportion of COVID-19 patients (83.33%) have microthrombosis in their lungs, compared to much lower levels in the CONTROL (9%) and H1N1 (10%) groups. The study suggests that SARS-CoV-2 can lead to uncontrolled thrombogenic activity and pose a threat to life, whereas other infections such as Influenza A can also cause blood vessel dysfunction [ 7 , 8 ]. The final formation of microthrombi has multiple complex pathways that are still being studied and elucidated, but COVID-19 is already recognized as a disease that is characterized by hypercoagulability, inflammation, and vascular dysfunction.…”

“…The influenza A infection of endothelial cells also causes a significant modulation of the Inhibitor of Activation of the Plasminogen-1 (PAI-1). Pronounced changes in the degree of PAI-1 expression in endothelial cells confirm the ability of the Influenza A virus H1N1 subtype (H1N1pdm09) to cause intravascular coagulation [ 7 , 8 ].…”

Vascular dysfunction in COVID-19 patients: update on SARS-CoV-2 infection of endothelial cells and the role of long non-coding RNAs

“…In these studies, commercially available pulmonary, aortic, umbilical, or cardiac primary ECs were applied. So far, the results have been controversial, emphasizing the necessity of further research to clarify the impact of SARS-CoV-2 on ECs, particularly in CVD patients, in order to account for conditions of increased oxidative stress, inflammatory cytokines, reduced vasodilation and antithrombotic features, reflecting atherosclerotic changes within the arterial wall [13,135,[158][159][160].…”