Casting NETs in the failing heart
White blood cells are essential for fighting infection using specific killing mechanisms. However, when these processes get activated in the absence of infection, this can cause disease. One of the ways that white blood cells try to fight infection is by sending out neutrophil extracellular traps (NETs), ejecting their DNA lined with proteins that can kill bacteria. These same proteins also damage healthy blood vessels and cause them to become activated, which binds platelets and can lead to small blood clots. Activated platelets are one way that white blood cells can be stimulated to make NETs, and therefore this is a vicious cycle. This study aims to study this interaction between neutrophils and platelets in a specific disease context: development of heart failure. Heart failure occurs when the heart is not able to properly pump blood to the rest of the body. This can happen when the heart muscle is damaged and tries to repair itself, leaving widespread scar tissue (fibrosis) that doesn't allow the heart muscle to beat properly. We will look at the ways in which NETs can contribute to this tissue damage, both how the NETs are formed, and what are the consequences. We will also look for markers of NETs in blood from patients at risk for developing heart failure, to see if our experimental models are relevant in patients. From this research, we hope to gain insights into how this process can be treated in order to develop better therapeutics and diagnostics for patients.