Role of cyclophilins and other EMMPRIN-ligands for platelet function and platelet-monocyte interaction

血小板是炎症心血管过程的中心调节器。当被激活时，血小板会释放各种促炎物质，包括亲环素。细胞外亲环素A和B可以通过细胞外基质金属蛋白酶诱导因子EMMPRIN在单核细胞中诱导致炎途径。在目前的资助期，我们可以证明细胞内CyPA是血小板钙稳态的重要调节因子。因此，缺乏CyPA的小鼠几乎可以预防动脉血栓形成。除了它在血小板内的重要作用外，我们还可以描述细胞外CyPA对血小板活化的重要影响。我们目前的初步数据表明，除了EMMPRIN之外，可能还有其他受体参与了CyPA的激活过程。此外，其他阻尼剂(危险相关的分子模式)可以与EMMPRIN结合，反之亦然。在接下来的资助期间，我们将描述这些新的相互作用，并阐明它们在血小板-单核细胞相互作用中的影响。最后，我们打算在患者队列中评估我们的实验数据。基于这些发现，可以开发新的抗血栓物质。

Platelets are central regulators of inflammatory cardiovascular processes. Upon activation platelets release a variety of pro-inflammatory substances including cyclophilins. Extracellular Cyclophilin A and B can induce proinflammatory pathways in monocytes via the Extracellular Matrix Metallo proteinase Inducer EMMPRIN. In the current funding period we could show that intracellular CyPA is a crucial regulator of platelets Ca2+ homeostasis. Thus, mice lacking CyPA are nearly protected from arterial thrombosis. In addition to its important intracellular role in platelets we could also describe the important influence of extracellular CyPA on platelet activation. Our current preliminary data show that may other receptors than EMMPRIN could be involved in CyPAactivation processes. Furthermore other DAMPs (¿danger associated molecular patterns¿) can bind to EMMPRIN vice versa. In the following funding period they we will characterize these novel interactions and clarify their influence in platelet-monocyte interaction. Finally we intend to evaluate our experimental data in patient cohorts. Based on these findings novel antithrombotic substances could be developed.