Faculty of Medicine, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
Cardiology Department, East and North Hertfordshire NHS Trust, Stevenage, Hertfordshire SG1 4AB, UK.
Int J Mol Sci. 2021 May 12;22(10):5135. doi: 10.3390/ijms22105135.
The extent and duration of occlusive thrombus formation following an arterial atherothrombotic plaque disruption may be determined by the effectiveness of endogenous fibrinolysis. The determinants of endogenous fibrinolysis are the subject of much research, and it is now broadly accepted that clot composition as well as the environment in which the thrombus was formed play a significant role. Thrombi with a high platelet content demonstrate significant resistance to fibrinolysis, and this may be attributable to an augmented ability for thrombin generation and the release of fibrinolysis inhibitors, resulting in a fibrin-dense, stable thrombus. Additional platelet activators may augment thrombin generation further, and in the case of coronary stenosis, high shear has been shown to strengthen the attachment of the thrombus to the vessel wall. Neutrophil extracellular traps contribute to fibrinolysis resistance. Additionally, platelet-mediated clot retraction, release of Factor XIII and resultant crosslinking with fibrinolysis inhibitors impart structural stability to the thrombus against dislodgment by flow. Further work is needed in this rapidly evolving field, and efforts to mimic the pathophysiological environment in vitro are essential to further elucidate the mechanism of fibrinolysis resistance and in providing models to assess the effects of pharmacotherapy.
动脉粥样硬化血栓斑块破裂后闭塞性血栓形成的程度和持续时间可能取决于内源性纤维蛋白溶解的效果。内源性纤维蛋白溶解的决定因素是许多研究的主题，现在广泛接受的观点是，血栓的组成以及血栓形成的环境都起着重要作用。血小板含量高的血栓显示出对纤维蛋白溶解的显著抵抗力，这可能归因于凝血酶生成能力增强以及纤维蛋白溶解抑制剂的释放，导致纤维蛋白致密、稳定的血栓。其他血小板激活剂可能进一步增强凝血酶生成，在冠状动脉狭窄的情况下，高剪切力已被证明可增强血栓与血管壁的附着。中性粒细胞胞外诱捕网有助于抵抗纤维蛋白溶解。此外，血小板介导的血栓回缩、因子 XIII 的释放以及与纤维蛋白溶解抑制剂的交联，赋予血栓结构稳定性，使其免受血流冲刷而脱落。在这个快速发展的领域还需要进一步的研究，努力模拟体外病理生理环境对于进一步阐明纤维蛋白溶解抵抗的机制以及提供评估药物治疗效果的模型至关重要。
