Grant: Travel Awards - Institute Community Support

Thrombosis (pathological blood clot formation) is the most frequent cause of mortality worldwide. Von Willebrand factor (VWF) is a protein in the blood that helps blood clot formation by binding platelets (the primary cellular component of clots) to each other and to the blood vessel wall. High VWF levels in the blood increases the risk of thrombosis and is associated with diseases such as strokes. Inflammation is part of the immune response mounted against a harmful stimulus and it has been shown that inflammation increases VWF levels in the blood. However, the specific mechanism for this increase remains unclear. A class of white blood cells known as neutrophils participate in the inflammatory response and can release web-like structures in response to indicators of cell death and infections. These structures are called neutrophil extracellular traps (NETs) and consist of a meshwork of DNA and proteins that act like a net to localize the stimulus. We proposed that VWF and DNA may provide a mechanistic link between hemostasis and inflammation. Our investigations showed that in aging, a state of chronic inflammation, plasma levels of VWF and DNA were correlated in humans and mice. In septic patients and a mouse model of sepsis, representing acute inflammation, although VWF and DNA levels increased they were not correlated. Obesity is also associated with a low-grade chronic inflammatory state and in a diet-induced obese mouse model VWF levels increased but DNA levels did not change. When VWF levels were both above and below physiological (without the induction of inflammation) there was no change in DNA concentration. Furthermore, injecting histone (another component of NETs) but not DNA into mice induced VWF release. Therefore, VWF and DNA were correlated in aging but not sepsis or obesity models. This association may be dependent on NET components causing VWF release or another underlying inflammatory mechanism affecting VWF and DNA levels.