Scientists at the RCSI University of Medicine and Health Sciences in Dublin, Ireland, have discovered a new role for the blood clotting protein, von Willebrand Factor (VWF), that could lead to the development of new treatments for patients with inflammatory and blood clotting disorders.

The team published its study “von Willebrand factor links primary hemostasis to innate immunity” in Nature Communications, which describes how the researchers found that VWF plays an important role in regulating immune responses at sites of blood vessel injury. This means that the protein has a newly discovered role in repairing damaged blood vessels in addition to its role in blood clotting.

Deficiency in VWF is called von Willebrand disease and 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 the protein in their blood are at risk of developing serious blood clots. For example, high VWF levels have been implicated in the unusual blood clots seen in the lungs of patients with severe COVID-19.

This research shows, for the first time, that VWF not only regulates blood clotting at the site of damage but also triggers local immune responses. Understanding this new biological role for VWF in regulating inflammatory responses may offer the 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.

“The plasma multimeric glycoprotein von Willebrand factor (VWF) plays a critical role in primary hemostasis by tethering platelets to exposed collagen at sites of vascular injury. Recent studies have identified additional biological roles for VWF, and in particular, suggest that VWF may play an important role in regulating inflammatory responses. However, the molecular mechanisms through which VWF exerts its immuno-modulatory effects remain poorly understood,” wrote the investigators.

“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. In addition, VWF binding also drives macrophage M1 polarization and shifts macrophage metabolism towards glycolysis in a p38-dependent manner. “Cumulatively, our findings define an important biological role for VWF in modulating macrophage function, and thereby establish a novel link between primary hemostasis and innate immunity.”

Lead author of the research, James O’Donnell, PhD, director of the Irish Centre for Vascular Biology at the RCSI School of Pharmacy and Biomolecular Sciences, said that “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. 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.”

The research was conducted by RCSI in collaboration with Trinity College Dublin and the National Coagulation Centre in St. James’s Hospital, Dublin.