Cellular Mediators Linking Inflammation and Thrombosis

Thrombosis is a hallmark of life-threatening cardiovascular diseases, such as myocardial infarction, stroke or thromboembolism representing major causes of death in the Western civilization. In the established view, thrombosis is triggered by cascades of regulated protein interactions that result in the formation of fibrin. However, a novel view understands this phenomenon not only as activation and clotting of plasmatic coagulatory proteins, but as a dynamic interaction of cells and proteins of the blood system, which is strongly linked to inflammatory processes. The present funding application represents the collaborative effort of excellent research groups to provide a new view of thrombosis integrating the role of inflammatory processes thereby building up new strategies for therapeutic interventions. To that end, we intend to establish a consortium of interdisciplinary scientists, ranging from basic researchers to hospital clinicians, all of them based at the Medical University of Vienna. In a collaborative alliance of the current groups and with additional funding for 22 scientists and their respective material needs, we plan to study the roles of platelets, microparticles, leukocytes and endothelial cells in the course of inflammation-associated thrombosis. The specific aims of our consortium are: To identify and characterize pro-inflammatory roles of platelets and microparticles as a basis for novel anti- thrombotic therapies; To elucidate the mechanisms by which activated endothelial cells and leukocytes contribute to the process of thrombosis in diseases with aberrant coagulation states such as myocardial infarcts, stroke or venous thromboembolism; To establish a comprehensive bio-repository of patient samples and a corresponding electronic database allowing for a more detailed analysis of biomarkers and their correlation with disease progression.