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血栓形成和心血管疾病中的凝血因子和蛋白酶途径。

Coagulation factor and protease pathways in thrombosis and cardiovascular disease.

机构信息

Dr. Pablo García de Frutos, Institute of Biomedical Research of Barcelona (IIBB-CSIC), C/Roselló 161, 08036 Barcelona, Spain, Tel.: +34 933632382, E-mail:

出版信息

Thromb Haemost. 2017 Jun 28;117(7):1265-1271. doi: 10.1160/TH17-02-0079. Epub 2017 Jun 8.

Abstract

The biochemical characterisation of the proteolytic pathways that constitute blood coagulation was one of the most relevant achievements in biomedical research during the second half of the 20th century. Understanding these pathways was of crucial importance for improving global health through application in haemostasis and thrombosis pathologies. Immediately after the cloning of the genes corresponding to these proteins, mutations were discovered in them that were associated with imbalances in haemostasis. Later, the importance of coagulation pathways in other pathological processes was demonstrated, such as in atherosclerosis and inflammation, both essential processes involved in vascular disease. In the present review we evaluate the concepts that have allowed us to reach the integrated vision on coagulation that we have today. The thrombo-inflammation model encompassing these aspects includes a pivotal role for the proteases of the coagulation pathway as well as the regulatory proteins thereof. These concepts illustrate the importance of the coagulation cascade in cardiovascular pathology, not only in thrombotic processes, but also in atherosclerotic processes and in the response to ischaemia-reperfusion injury, making it a central mechanism in cardiovascular disease.

摘要

凝血途径中蛋白水解途径的生物化学特征是 20 世纪后半叶生物医学研究中最相关的成就之一。通过在止血和血栓形成病理学中的应用,理解这些途径对于改善全球健康至关重要。在这些蛋白质的基因被克隆后,立即发现了与止血失衡相关的突变。后来,凝血途径在其他病理过程中的重要性得到了证明,如动脉粥样硬化和炎症,这两个过程都是血管疾病中必不可少的。在本综述中,我们评估了使我们能够达到今天对凝血的综合认识的概念。包含这些方面的血栓炎症模型包括凝血途径的蛋白酶及其调节蛋白的关键作用。这些概念说明了凝血级联在心血管病理学中的重要性,不仅在血栓形成过程中,而且在动脉粥样硬化过程中和对缺血再灌注损伤的反应中,使其成为心血管疾病的中心机制。

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