Laboratory for Clinical Thrombosis and Haemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, UNS50: Box8, 6200, MD, Maastricht, The Netherlands,
Curr Atheroscler Rep. 2013 Nov;15(11):363. doi: 10.1007/s11883-013-0363-3.
Thrombin is a pleiotropic enzyme that regulates hemostasis and nonhemostatic functions, including an array of actions within and on the vasculature. Physiologically, thrombin generation serves mainly to protect against thrombosis, but also to maintain vascular endothelial integrity. This protective effect is mediated in part through generation of anticoagulant enzymes, including activated protein C, formed on the action of thrombin on the endothelial receptor thrombomodulin. Partly, thrombin's vascular effects are effectuated through interaction with protease-activated receptors on various cell types. Pathophysiologically, downregulation and shedding of anticoagulant-acting receptors such as thrombomodulin and endothelial protein C receptor may contribute to a shift in activities of thrombin towards thrombogenic and proinflammatory actions. This shift may typically occur in the process of atherosclerosis, leading to a proatherogenic direction of the effects of thrombin. Therapeutically, the long-term inhibition of thrombin may create new ways of reducing atherosclerosis burden, altering the plaque phenotype.
凝血酶是一种多功能酶，调节止血和非止血功能，包括血管内和血管上的一系列作用。在生理上，凝血酶的产生主要用于防止血栓形成，但也用于维持血管内皮完整性。这种保护作用部分是通过生成抗凝酶来介导的，包括在凝血酶对内皮受体血栓调节蛋白的作用下形成的活化蛋白 C。部分凝血酶的血管作用是通过与各种细胞类型上的蛋白酶激活受体相互作用来实现的。在病理生理学上，抗凝作用受体如血栓调节蛋白和内皮蛋白 C 受体的下调和脱落可能导致凝血酶的活性向血栓形成和促炎作用转移。这种转变通常发生在动脉粥样硬化过程中，导致凝血酶的作用朝着促动脉粥样硬化的方向发展。在治疗上，长期抑制凝血酶可能会为减少动脉粥样硬化负担、改变斑块表型开辟新的途径。
