Pathophysiology Section, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Department of Diagnostic Pathology, University of Miyazaki Hospital, University of Miyazaki, Miyazaki, Japan.
Pathol Int. 2020 Jun;70(6):309-322. doi: 10.1111/pin.12921. Epub 2020 Mar 13.
Atherothrombosis is a leading cause of cardiovascular mortality and morbidity worldwide. The underlying mechanisms of atherothrombosis comprise plaque disruption and subsequent thrombus formation. Arterial thrombi are thought to mainly comprise aggregated platelets as a result of high blood velocity. However, thrombi that develop on disrupted plaques comprise not only aggregated platelets, but also large amounts of fibrin, because plaques contain large amount of tissue factor that activate the coagulation cascade. Since not all thrombi grow large enough to occlude the vascular lumen, the propagation of thrombi is also critical in the onset of adverse vascular events. Various factors such as vascular wall thrombogenicity, local hemorheology, systemic thrombogenicity and fibrinolytic activity modulate thrombus formation and propagation. Although the activation mechanisms of platelets and the coagulation cascade have been intensively investigated, the underlying mechanisms of occlusive thrombus formation on disrupted plaques remain obscure. Pathological findings derived from humans and animal models of human atherothrombosis have uncovered pathophysiological processes during thrombus formation and propagation after plaque disruption, and novel factors have been identified that modulate the activation of platelets and the coagulation cascade. These findings have also provided insights into the development of novel drugs for atherothrombosis.
动脉粥样硬化血栓形成是全世界心血管死亡率和发病率的主要原因。动脉粥样硬化血栓形成的潜在机制包括斑块破裂和随后的血栓形成。由于血流速度高，人们认为动脉血栓主要由聚集的血小板组成。然而，在破裂斑块上形成的血栓不仅包含聚集的血小板，还包含大量的纤维蛋白，因为斑块含有大量的组织因子，可激活凝血级联反应。由于并非所有血栓都长到足以阻塞血管腔，因此血栓的传播在不良血管事件的发生中也至关重要。各种因素，如血管壁血栓形成性、局部血液流变学、全身血栓形成性和纤维蛋白溶解活性，调节血栓形成和传播。尽管血小板和凝血级联的激活机制已得到深入研究，但破裂斑块上闭塞性血栓形成的潜在机制仍不清楚。源自人类和人类动脉粥样硬化动物模型的病理发现揭示了斑块破裂后血栓形成和传播过程中的病理生理过程，并鉴定出了调节血小板和凝血级联激活的新因子。这些发现也为动脉粥样硬化血栓形成的新型药物的开发提供了思路。
