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Monitoring Changes in Human Umbilical Vein Endothelial Cells upon Viral Infection Using Impedance-Based Real-Time Cell Analysis
Published on: May 5, 2023
Endothelial cell activation, Weibel-Palade body secretion, and enhanced angiogenesis in severe COVID-19
Ellie Karampini1, Helen Fogarty1, Stephanie Elliott1
1Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
Insights
Severe COVID-19 activates endothelial cells (ECs), increasing Weibel-Palade body proteins like von Willebrand factor (VWF) and angiopoietin-2 (Angpt-2). This EC activation promotes angiogenesis and correlates with disease severity.
Area of Science:
- Vascular Biology
- Infectious Diseases
- Immunology
Background:
- Severe COVID-19 is linked to endothelial cell (EC) activation, contributing to immunothrombosis and microvascular occlusion.
- The precise mechanisms by which SARS-CoV-2 induces EC activation and damage are not fully understood.
Purpose of the Study:
- To investigate EC activation in COVID-19 patients.
- To determine the role of Weibel-Palade body proteins in COVID-19 pathogenesis.
Main Methods:
- Recruited 39 patients with confirmed COVID-19.
- Measured Weibel-Palade body biomarkers (von Willebrand factor [VWF], angiopoietin-2 [Angpt-2], osteoprotegerin) and soluble thrombomodulin (sTM).
- Assessed EC activation and angiogenesis with and without COVID-19 plasma incubation.
Main Results:
- Patients with acute COVID-19 showed elevated plasma VWF, Angpt-2, osteoprotegerin, and sTM.
- Increased sTM and Weibel-Palade biomarkers correlated with COVID-19 severity.
- COVID-19 plasma incubation enhanced EC VWF secretion, Angpt-2 expression, and angiogenesis.
Conclusions:
- Acute SARS-CoV-2 infection causes multifactorial EC activation and thrombomodulin loss.
- Increased Angpt-2 expression promotes a proangiogenic state in COVID-19.
- These findings elucidate mechanisms of EC dysfunction in severe COVID-19.
Background:
Severe COVID-19 is associated with marked endothelial cell (EC) activation that plays a key role in immunothrombosis and pulmonary microvascular occlusion. However, the biological mechanisms through which SARS-CoV-2 causes EC activation and damage remain poorly defined.
Objectives:
We investigated EC activation in patients with acute COVID-19, and specifically focused on how proteins stored within Weibel-Palade bodies may impact key aspects of disease pathogenesis.
Methods:
Thirty-nine patients with confirmed COVID-19 were recruited. Weibel-Palade body biomarkers (von Willebrand factor [VWF], angiopoietin-2 [Angpt-2], and osteoprotegerin) and soluble thrombomodulin (sTM) levels were determined. In addition, EC activation and angiogenesis were assessed in the presence or absence of COVID-19 plasma incubation.
Results:
Markedly elevated plasma VWF antigen, Angpt-2, osteoprotegerin, and sTM levels were observed in patients with acute COVID-19. The increased levels of both sTM and Weibel-Palade body components (VWF, osteoprotegerin, and Angpt-2) correlated with COVID-19 severity. Incubation of COVID-19 plasma with ECs triggered enhanced VWF secretion and increased Angpt-2 expression, as well as significantly enhanced in vitro EC tube formation and angiogenesis.
Conclusion:
We propose that acute SARS-CoV-2 infection leads to a complex and multifactorial EC activation, progressive loss of thrombomodulin, and increased Angpt-2 expression, which collectively serve to promote a local proangiogenic state.
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