Study explores how blood vessel structure may influence bleeding disorders

New research from Imperial suggests that changes in blood vessel structure may contribute to bleeding disorders.

The study, published in Blood and led by researchers at Imperial’s National Heart and Lung Institute, examined how bleeding can be the results of defects in blood vessels as well as blood clotting. They focus on a protein called von Willebrand factor (VWF), which is essential to stop bleeding from the skin or mucosal tissues. Patients with lack or dysfunction of VWF (called von Willebrand Disease or VWD) suffer from excessive bleeding. VWD is the most common bleeding disorder affecting ~ 1% of the population.   

The researchers explored how blood vessels and clotting interact to control bleeding. They focused on gastrointestinal (GI) bleeding, a clinically important and difficult-to-treat problem that is particularly common in older adults and in patients with VWD. GI bleeding is often associated with fragile blood vessels in the gut; thus bleeding can persist even when abnormalities in blood clotting are treated.   

Using a combination of patient-derived cells, in vivo studies and a newly developed vascularised “gut-on-chip” model, the team showed that loss of VWF disrupts the stability of blood vessels. They identified dysregulation of Angiopoietin-2 (ANGPT2), a protein involved in blood vessel remodelling, as a key driver of this effect. Importantly, blocking ANGPT2 with a drug already tested in humans restored normal vessel structure in the “gut-on-chip” model, suggesting a potential new therapeutic avenue for these patients. 

Professor Anna Randi, Professor of Cardiovascular Medicine and senior author of the study, said, “This work grew directly from an unmet clinical need in patients with chronic gastrointestinal bleeding. By bringing together vascular biology, haematology and bioengineering, we’ve been able to identify a new mechanism and a potential therapeutic target, while also broadening how we think about the role of blood vessels in bleeding.” 

Dr Adela Constantinescu-Bercu, Postdoctoral Research Associate and lead author added, “Developing a personalised, vascularised organ-on-chip model gives us a powerful tool to study disease mechanisms and test treatments in a way that closely reflects what happens in patients.” 

These findings suggest that pathways regulating blood vessel stability warrant further investigation as potential contributors to chronic bleeding. Although the study focused on the gut, the researchers note that similar blood vessel-related mechanisms could be relevant to other bleeding conditions. Fragile or abnormal blood vessels are implicated in a range of disorders and understanding how vascular structure is maintained may have broader implications beyond gastrointestinal bleeding.