Blood Clotting Protein Found to Trigger Inflammation

Researchers in Dublin have found that blood clotting protein von Willebrand Factor (VWF) also plays a role in regulating immune response at the site of blood vessel injury, presenting an opportunity to develop entirely new treatment options for patients with inflammatory and blood clotting disorders, such as von Willebrand Disease, deep vein thrombosis and myocardial infarction.

VWF deficiency, also called von Willebrand Disease, occurs in about 1 in 1,000 people in Ireland. People with this condition have increased risk of serious heavy bleeding. In contrast, people with high levels of VWF in their blood are at risk of developing serious blood clots. For example, very high VWF levels have been implicated in the unusual blood clots seen in the lungs of patients with severe COVID-19.

Published recently in Nature Communications, the study by RCSI University of Medicine and Health Sciences in collaboration with Trinity College Dublin and the National Coagulation Centre in St James’s Hospital, Dublin shows for the first time that VWF triggers local immune responses.  “In this study, we report that VWF binding to macrophages triggers downstream MAP kinase signaling, NF-κB activation and production of pro-inflammatory cytokines and chemokines,” according to the study. “In addition, VWF binding also drives macrophage M1 polarization and shifts macrophage metabolism towards glycolysis in a p38-dependent manner.” Cumulatively, the findings define an “important biological role” for VWF in modulating macrophage function, and thereby establish a novel link between primary hemostasis and innate immunity.

“For more than 50 years, it has been known that von Willebrand factor plays a key role in preventing bleeding by acting as a glue at the site of injury,” says lead author Professor James O’Donnell, Director of the Irish Centre for Vascular Biology at RCSI School of Pharmacy and Biomolecular Sciences. “This research now helps us to further understand the role that VWF plays in linking blood coagulation and inflammation and thereby paves the way for the development of new treatments.”