Intracellular signaling in platelets and the role of platelet lipid metabolism and secretome in platelet-mediated vascular, valvular and myocardial thrombo-inflammation

本研究的目的是确定血小板中的分子信号级联，它与血小板介导的血管、瓣膜和心肌炎症过程以及动脉和静脉血栓的形成密切相关。血小板中血栓炎症的多层次过程(细胞内、膜相关和细胞外/分泌)将被更详细地描述，并使用各种体内模型来分析它们的意义。除了血小板内的信号级联作用外，还研究了血小板脂体(第二信使分子的产生和血小板膜的修饰)以及由血小板释放的信使物质(脂类、微RNA和趋化因子)在血小板与炎症细胞相互作用，特别是在心肌以及血管炎症和血栓形成过程中的重要性。基于对心血管血栓炎症过程的更深入的了解，预防性干预方案以及新的生物标志物和更具选择性的抗血栓治疗策略的开发将使止血和血管完整性不受影响。

This research project aims to identify molecular signal cascades in platelets, which are significantly involved in platelet-mediated processes of vascular, valvular and myocardial inflammation, as well as in the development of arterial and venous thrombosis. The multi-layered processes of thrombo-inflammation in platelets (intracellular, membrane-related and extracellular/secretory) are to be characterized in more detail and their significance analyzed using various in vivo models. In addition to intracellular signal cascades in platelets, the platelet lipidome (generation of second messenger molecules and modification of the platelet membrane) and the importance of messenger substances released by the platelets (lipids, microRNAs and chemokines) in terms of their importance for the platelet interaction with inflammatory cells and especially for processes of myocardial as well as vascular inflammation and thrombosis are examined. Based on a deeper understanding of the processes of cardiovascular thrombo-inflammation, preventive intervention options, as well as new biomarkers and the development of more selective anti-thrombotic therapy strategies, which leave hemostasis and vascular integrity unaffected, are to be developed.