A team of scientists has found out how the proteins of the SARS-CoV-2 coronavirus affect the vascular system. By affecting the endothelial cells of the vascular walls, they cause increased coagulation and inflammation.
In addition to the respiratory tract, the new coronavirus affects other body systems, including the entire vascular network. There is an increasing opinion among experts that COVID-19 can be considered equally as a respiratory and vascular disease.
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Researchers at Tel Aviv University have found that SARS-CoV-2 proteins affect vascular permeability by attacking endothelial cells.
After the initial phase of viral infection, about 30 percent of hospitalized patients develop severe illness with progressive lung damage and hypertrophied immune response, which manifests itself as a sharp drop in blood oxygen levels, a cytokine storm, and heart and kidney failure. According to the authors, many of these pathologies are associated with increased blood coagulation and vascular dysfunction.
The SARS-CoV-2 genome encodes 29 proteins that determine the manifestations and symptoms of COVID-19. To see the effect of coronavirus proteins on endothelial cells, scientists cloned and expressed 26 of these proteins in human umbilical vein cells.
Based on the endothelial response to overexpression of each protein, the authors accurately determined how each of the SARS-CoV-2 proteins, independently of the others, affects the change in the endothelial barrier of blood vessels, increased coagulation, inflammation and the release of cytokines.
As a result of the study, scientists found that 70 percent of coronavirus proteins stimulate significant changes in endothelial permeability, which are associated with several factors:
- one with a direct effect on the cells lining the inner surface of the vessels, and causing endothelial dysfunction;
- second with lysis, or dissolution of endothelial cells and their death;
- third with the rejection of human angiotensin-converting enzyme 2 (hACE2) by viral proteins that promote vascular permeability.
In addition, the researchers believe that an overreaction of the immune system, in which a combination of immune cells and neutrophils occurs, causes the production of reactive oxygen species, inflammatory cytokines, and vasoactive molecules, and the deposition of hyaluronic acid causes changes in endothelial junctions, increased vascular permeability, blood leakage, and coagulation.
Based on the results of the study, the authors determined which of the viral proteins play a decisive role in the physiological response to viral infection and, based on this, prepared recommendations for the development of drugs aimed at suppressing these proteins.
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The research results have been published on the bioRxiv.