OC 05.5 - Endothelial cell activation, Weibel-Palade body secretion and enhanced angiogenesis in severe COVID-19

Saturday, July 9, 2022

2:00 PM – 2:15 PM

Location: ICC Capital Suite Room 8&9

Presentation Format: In-Person

Presenting Author(s)

Ellie Karampini, PhD

Post Doctoral Researcher
Royal College of Surgeons in Ireland, RCSI Dublin
Dublin, Dublin, Ireland

Co-Author(s)

SE

Stephanie Elliott

Research Assistant
Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin 2, Ireland
Dublin, Carlow, Ireland
Helen Fogarty, MB BAO BCh MSc MRCPI

Haematology SpR and Wellcome Trust/HRB ICAT Fellow
Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin Ireland
Dublin, Dublin, Ireland
JO

Jamie M. O’Sullivan, PhD

StAR Research Lecturer
Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
Dublin, Dublin, Ireland
CB

Colm Bergin

Professor
St James's Hospital
Dublin, Dublin, Ireland
CN

Cliona Ni Cheallaigh

Consultant in Infectious Diseases
Department of Infectious Diseases, St James’s Hospital, Dublin, Ireland.
Dublin, Dublin, Ireland
MB

Mary Byrne

Coagulation Laboratory Chief
National Coagulation Centre, St James's Hospital, Dublin
Dublin, Dublin, Ireland
IM

Ignacio Martin-Loeches

Professor of Intensive Care Medicine
Department of Intensive Care Medicine, St James’s Hospital, Dublin, Ireland
Dublin, Dublin, Ireland
PM

Patrick W. Mallon

Professor
UCD
Dublin, Dublin, Ireland
GC

Gerard F. Curley

Professor
Royal College of Surgeons in Ireland, RCSI Dublin
Dublin, Dublin, Ireland
SG

Siobhan Glavey

Professor
Royal College of Surgeons in Ireland, RCSI Dublin
Dublin, Dublin, Ireland
Roger J.S. Preston, PhD

Principal Investigator, Lecturer in Vascular Biology
Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin 2, Ireland
Dublin, Dublin, Ireland
SW

Soracha Ward

Postdoctoral
RCSI
Dublin, Dublin, Ireland
JO

James S. O'Donnell, MB, PhD

Professor of Haematology
Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland,Dublin, Ireland
Dublin, Dublin, Ireland

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.

Aims: 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.

Methods: 39 patients with confirmed COVID-19 were recruited. Weibel-Palade body biomarkers [von Willebrand factor (VWF), angiopoietin-2 (Ang-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, Ang-2, OPG and sTM levels were observed in acute COVID-19 patients. The increased levels of both sTM and WPB components (VWF, OPG and Ang-2) correlated with COVID-19 severity. Incubation of COVID-19 plasma with ECs triggered enhanced VWF secretion and increased Ang-2 expression (Figure 1). In keeping with the autopsy reports of intussusceptive angiogenesis, treatment with COVID-19 plasma also caused significantly increased EC angiogenesis (Figure 1).

Conclusion(s): We propose that as COVID-19 develops, progressive loss of TM and increased sTM, as well as increased Ang-2 expression result in loss of EC quiescence, WPB exocytosis, and a local pro-angiogenic state.