Abstract
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 in particular focused on how proteins stored within Weibel-Palade bodies (WPBs) may impact key aspects of disease pathogenesis.
Patients and Methods
39 patients with confirmed COVID-19 were recruited. Weibel-Palade body biomarkers [von Willebrand factor (VWF), angiopoietin-2 (Angpt-2) and osteoprotegerin (OPG)] 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:Ag, Angpt-2, osteoprotegerin and sTM levels were observed in acute COVID-19 patients. The increased levels of both sTM and WPB 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.
Conclusions
We propose that acute SARS-CoV-2 infection leads to a complex and multifactorial EC activation, progressive loss of TM, as well as increased Angpt-2 expression which collectively serve to promote a local pro-angiogenic state.
