microRNAs as predictive biomarkers of venous thromboembolism

Venous thrombosis is one of the most common vascular diseases with 1 to 2 cases per 1000 persons per year. Thrombosis occurs when the blood clots too strongly or in the wrong place. As a result, a blood clot forms (thrombus), which can lead to a partial or complete closure of a blood vessel. Venous thrombosis is a chronic disease as it tends to recur (25-30% in the first 5 years) which causes death in about 4% of patients. Recurrent thrombosis can effectively be prevented by anticoagulant treatment albeit at the cost of bleeding. The current available risk scores for the prediction of future thrombosis are not accurate enough which makes it difficult to decide if long-term anticoagulant is justified. Therefore intensive research is required to find new strategies for assessing the individual risk of a patient to experience another thrombosis. In this context, short nucleic acids, so-called microRNAs, are of particular interest. microRNAs are encoded in our genome and fulfill important tasks in the control of biological processes by binding to messenger(m)RNA molecules that form the template for proteins. After binding, the production of a functional protein is modulated, what consequently changes the physiological properties of the affected cells. For basic and clinical research microRNAs are attractive as they can be used as blood-based biomarkers leading to a better understanding of the underlying pathomechanisms. The central hypothesis of our research project is that individual microRNAs differ quantitatively in the blood from thrombosis patients and healthy individuals where they essentially influence the pathogenesis of thrombosis. Therefore, the aim of our study is to characterize microRNA signatures in thrombosis patients which can be used as biomarkers to predict thrombosis. Our work is a part of the Austrian Study on Recurrent Venous Thromboembolism, one of the largest studies worldwide to investigate the impact of clinical and laboratory markers on the risk of recurrent thrombosis. With the help of modern laboratory analysis, we want to characterize the microRNA signatures in the plasma of thrombosis patients and healthy individuals. Since microRNAs are directly linked to cellular activity, thrombosis-related microRNAs can discriminate between "ill" and "healthy". In addition, we want to reveal the cellular function of selected thrombosis-associated microRNAs. Our special focus lies on the elucidation of unknown microRNA-mRNA interactions. With the planned research project, we will provide novel predictive biomarkers which could optimize current risk assessment models for venous thrombosis. Moreover, microRNAs will improve our understanding of the molecular mechanisms that govern venous thrombosis development.