Cardiovascular diseases like myocardial infarction, stroke, and venous thromboembolism, as well as associated complications are still the leading cause of morbidity and mortality in the European Union, resulting in enormous health care costs. Although, it is well acknowledged that beside platelets the immune system plays a pivotal role in thrombus formation and cardiovascular conditions, the underlying molecular and signaling mechanisms are still poorly defined and cellular processes are not understood. Nevertheless, neutrophils were shown to significantly contribute to venous thrombosis and thromboembolism. Activated neutrophils are able to release decondensed chromatin in a process called Neutrophil Extracellular Trap formation (NETosis), which is well known to foster platelet activation and adhesion. Originally described as crucial part of the innate immune response against pathogens , NETosis is now understood as a main factor in venous thrombus formation and progression, which can be induced by local hypoxia, among other things. Just recently, NETosis was defined as a well-orchestrated process of cellular events, including cytoskeleton rearrangements, nuclear envelope breakdown and plasma membrane rupture .
For this reason, the overall objective of the underlying project is the investigation of new molecular targets in the NETosis process and their impact on venous thromboembolism. Molecules and signaling mechanisms that affect the nuclear envelope breakdown and plasma membrane rupture in neutrophils are in the focus of the research, since both processes are crucial hallmarks of NETosis. In the end, the project will help to identify new druggable targets and biomarkers associated with thrombo-inflammatory diseases.