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

亲环蛋白和其他 EMMPRIN 配体对血小板功能和血小板-单核细胞相互作用的作用

• 批准号: 208681624
• 负责人: Privatdozent Dr. Peter Seizer
• 金额: --
• 依托单位: Klinik für Innere Medizin II
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/208681624?language=en
• 关键词: Role; cyclophilins; other; EMMPRIN; ligands

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.

血小板是炎症性心血管过程的中枢调节因子。在活化时，血小板释放多种促炎物质，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剂EMMPRIN诱导单核细胞中的促炎症途径。在目前的资助期间，我们可以证明细胞内CyPA是血小板Ca2+稳态的重要调节剂。因此，缺乏CyPA的小鼠几乎不受动脉血栓形成的影响。除了其在血小板中的重要细胞内作用外，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，可能其他受体比EMMPRIN可能参与CyPA激活过程。此外，其他DAMP（危险相关分子模式）可以与EMMPRIN结合，反之亦然。在接下来的资助期内，我们将描述这些新的相互作用，并阐明它们对血小板-单核细胞相互作用的影响。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形成物质。

项目成果

Platelet-bound cyclophilin A in patients with stable coronary artery disease and acute myocardial infarction

• DOI: 10.3109/09537104.2015.1051466
• 发表时间: 2016-02-17
• 期刊: PLATELETS
• 影响因子: 3.3
• 作者: Seizer, Peter;Fuchs, Christian;Geisler, Tobias
• 通讯作者: Geisler, Tobias

TGFβ Is Specifically Upregulated on Circulating CD14++ CD16+ and CD14+ CD16++ Monocytes in Patients with Atrial Fibrillation and Severe Atrial Fibrosis

• DOI: 10.1159/000492873
• 发表时间: 2018-01-01
• 期刊: CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
• 作者: Heinzmann, David;Fuss, Stefan;Seizer, Peter
• 通讯作者: Seizer, Peter