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For Covid-19 patients with severe lung disease, targeting endothelial cells (cells that comprise the wall of blood vessels that regulate the exchange of oxygen between the airways and the bloodstream) may be a novel approach that restores blood pressure. normal lung function. This hypothesis arises from a study conducted by researchers from the Department of Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University and published in mBio, the leading journal of the American Society for Microbiology.
SARS-CoV-2 causes Covid-19, which is characterized by pulmonary edema, viral pneumonia, coagulopathy, inflammation, and other physiological abnormalities. SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) receptors to infect and damage the ciliated epithelial vascular cells of the upper respiratory tract. However, how SARS2 dysregulates vascular functions causing acute respiratory distress syndrome (ARDS) in Covid-19 patients remains an enigma.
Led by Erich Mackow, PhD, Professor of Microbiology and Immunology, the team of scientists sought to unravel this mechanism by investigating SARS-CoV-2 infection of human endothelial cells of the lung, brain, heart and kidney that are affected by COVID-19 patients.
“Claims that endothelial cells are infected by SARS-CoV-2 through ACE2 receptors have never been directly evaluated,” Mackow said. “Our research revealed that endothelial cells lack ACE2 receptors and that endothelial cells were only infected with SARS-CoV-2 after expressing ACE2 receptors on them. Since endothelial cell functions are deregulated by SARS-CoV- 2, these findings suggest a new regulatory mechanism that does not require viral infection. Instead, they suggest indirect activation of the endothelium, which could result from surrounding tissue damage, which could be the basis for future research to therapeutically target and restore normal responses. of endothelial cells “.
Mackow adds that his work focuses on both endothelial cells and ACE2 functions in Covid-19 disease to identify the mechanisms of capillary inflammation and aberrant coagulation within vessels. He explains that the research reveals a novel mechanism of endothelial clotting and inflammation observed in the lung and heart of COVID-19 patients.
“A transformative change in the mechanism of endothelial cell dysfunction, not the infection of the cells themselves, changes the way disease starts and the rationale for therapeutic targeting. If the endothelial cells are not directly infected or damaged , they can still direct inflammation and clotting just by being activated, “he concludes from the research results.
The team is working on how the virus can activate endothelial cells or in response to other SARS-CoV-2-infected lung cells that express ACE2.
Research suggests the potential to therapeutically target activation, rather than endothelial infection, as a strategy to resolve the coagulation and inflammatory symptoms of Covid-19.
Mackow emphasizes that further investigation of endothelial cells and downregulated ACE2 functions after SARS-CoV-2 infection is necessary to determine targets that could lead to a reduction in respiratory distress and symptoms of the patients with Covid-19.
The research is supported by an initial grant from Stony Brook University, along with additional funding from the Mathers Foundation and the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health: grant numbers RO1AI12901004, R21AI13173902 and R21AI15237201 .
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Materials provided by Stony Brook University. Note: content can be edited for style and length.
