Tissue-type plasminogen activator: a historical perspective and personal account
Tissue-type plasminogen activator: a historical perspective and personal account
复制标题
DOI：
10.1111/j.1538-7933.2004.00645.x
复制
发表时间：
2004-04-01
影响因子：
10.4
通讯作者：
Lijnen, HR
中科院分区：
文献类型：
--
作者：
Collen, D;Lijnen, HR
在过去的二十年里，组织型纤溶酶原激活剂(t-PA)作为主要的生理性纤溶酶原激活剂，已被开发为一种纤维蛋白特异性的溶栓剂，用于治疗各种血栓栓塞性疾病。这一发展的里程碑包括：第一次从子宫组织中纯化人t-PA，阐明了调节生理纤溶的相互作用，从而为纤维蛋白特异性纤溶酶原激活的概念提供了分子基础，第一次血栓形成的动物模型和对支持t-PA治疗潜力的患者的初步研究，重组t-PA的克隆和表达为大规模的临床应用提供了足够的数量，以及在大型多中心临床试验中证明了其治疗效果，主要是在急性心肌梗死(AMI)的患者，但也在大规模肺栓塞、缺血性中风、深静脉血栓形成和周围动脉闭塞的患者中。T-PA的转基因变体已被开发用于急性心肌梗死患者的团注给药。
Over the past two decades tissue-type plasminogen activator (t-PA), the main physiological plasminogen activator, has been developed as a fibrin-specific thrombolytic agent for the treatment of various thromboembolic diseases. Milestones in this development include: first purification of human t-PA from uterine tissue, elucidation of the interactions regulating physiological fibrinolysis, thus providing a molecular basis for the concept of fibrin-specific plasminogen activation, first animal models of thrombosis and pilot studies in patients supporting the therapeutic potential of t-PA, cloning and expression of recombinant t-PA providing sufficient amounts for large scale clinical use, and demonstration of its therapeutic benefit in large multicenter clinical trials, mainly in patients with acute myocardial infarction (AMI), but also in patients with massive pulmonary embolism, ischemic stroke, deep vein thrombosis and peripheral arterial occlusion. Genetically modified variants of t-PA have been developed for bolus administration in patients with AMI.