Laboratory for Clinical Thrombosis and Haemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, PO Box 616, UNS50 Box 8, 6200 MD Maastricht, The Netherlands.
Cardiovasc Res. 2014 Mar 1;101(3):344-51. doi: 10.1093/cvr/cvt343. Epub 2014 Jan 2.
Factor Xa and thrombin are well-known components of the coagulation cascade and have been proven to be viable targets for effective anticoagulation treatment. However, accumulating evidence suggests that these serine proteases are also crucial modulators of other cellular mechanisms through the activation of protease-activated receptor (PAR)-mediated signalling. The involvement of factor Xa, thrombin, and PARs in normal biological and pathophysiological processes has been recognized, and their potential implications have been explored in recent years. Both factor Xa and thrombin play significant roles in mediating cellular signalling effects associated with the initial development of atherosclerosis: a chronic inflammatory vascular disease. In addition, increased expression and activation of PARs may be associated with atrial fibrillation (AF) and AF-associated thromboembolism hypercoagulability. Both pathologies are associated with hypercoagulability, suggesting that the role of cellular effects of factor Xa and thrombin and of their specific inhibitors should be studied in relation to the prevention of thrombotic and pro-arrhythmic changes. This review examines the role of factor Xa-mediated and thrombin-mediated PAR activation in modulating cellular processes involved in atherosclerosis and AF and discusses the potential implication of direct factor Xa and thrombin inhibition on effects outside coagulation.
Xa 因子和凝血酶是凝血级联反应中众所周知的组成部分，已被证明是有效抗凝治疗的可行靶点。然而，越来越多的证据表明，这些丝氨酸蛋白酶也是其他细胞机制的关键调节剂，通过激活蛋白酶激活受体 (PAR) 介导的信号转导。Xa 因子、凝血酶和 PARs 参与正常的生物学和病理生理学过程已得到认可，近年来它们的潜在意义也得到了探讨。Xa 因子和凝血酶都在介导与动脉粥样硬化初始发展相关的细胞信号效应中发挥重要作用：一种慢性炎症性血管疾病。此外，PAR 的表达和激活增加可能与心房颤动 (AF) 和 AF 相关的血栓栓塞性高凝状态有关。这两种病理都与高凝状态有关，这表明应该研究 Xa 因子和凝血酶及其特定抑制剂的细胞作用，以预防血栓形成和致心律失常变化。这篇综述检查了 Xa 因子介导和凝血酶介导的 PAR 激活在调节参与动脉粥样硬化和 AF 的细胞过程中的作用，并讨论了直接抑制 Xa 因子和凝血酶对凝血以外的作用的潜在意义。
