Grant: Project Grant

Sepsis (ie. serious infections of the blood) can cause a vicious cycle of blood clot formation, inflammation, and cell death which may lead to multiple organ failure and even death. In Canada, there are approximately 90,000 patients with sepsis each year, with estimated mortality rates of up to 25%. Despite decades of sepsis research, there are no anti-sepsis drugs and the mortality rate of sepsis remains high. This suggests that some fundamental knowledge is lacking in our understanding of why sepsis kills patients. This project focuses on ADAMTS13, a molecule that helps to prevent harmful blood clots from forming during sepsis. The main function of ADAMTS13 is to "cut" a long, sticky protein called VWF into smaller less sticky pieces. During sepsis, the blood is prone to clotting due to high levels of VWF, so ADAMTS13 may be a new way to treat sepsis-induced blood clots. The main focus of this proposal is to study whether ADAMTS13 is a useful treatment for sepsis. We will use two animal models of sepsis (an abdominal model and a lung infection model) to help increase the applicability of our findings. We will study both biological sexes as well as young versus old mice. We will also explore strategies to make ADAMTS13 even more effective such as testing a "long-lasting" version of ADAMTS13. These studies have the potentail to open up new avenues to treat sepsis.