Endothelial cell activation, Weibel-Palade body secretion, and enhanced angiogenesis 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.
Health Research Board COVID-19 Rapid Response award; Award Number: COV19- 2020-086
3M Foundation to RCSI University of Medicine and Health Sciences
Wellcome Trust and the Health Research Board; Grant Number: 203930/B/16/Z
Health Service Executive National Doctors Training and Planning and the Health and Social Care, Research and Development Division Science Foundation Ireland; Grant Number: 20/COV/0038
National Children’s Research Centre Project Award; Award Number: C/18/1
CommentsThe original article is available at https://www.sciencedirect.com/
Published CitationKarampini E, et al. Endothelial cell activation, Weibel-Palade body secretion, and enhanced angiogenesis in severe COVID-19. Res Pract Thromb Haemost. 2023;7(2):100085.
Publication Date14 February 2023
- Irish Centre for Vascular Biology
- School of Pharmacy and Biomolecular Sciences
- Anaesthetics and Critical Care
- Beaumont Hospital
- Published Version (Version of Record)