Protein S: function, regulation, and clinical perspectives.
Protein S: function, regulation, and clinical perspectives.
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蛋白质S：功能、调节和临床前景。
DOI：
10.1097/moh.0000000000000663
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发表时间：
2021-09-01
影响因子：
3.2
通讯作者：
Nguyen T
中科院分区：
文献类型：
--
作者：
Majumder R;Nguyen T
这篇综述旨在促进对一种重要的血浆蛋白蛋白s的抗凝功能的理解。尽管经过40多年的研究，我们还没有完整的描述PS生物学，因为它与血液凝固的控制有关。然而，随着最近发现PS对FIXa的抑制作用，PS功能的图景变得更加清晰。PS介导的止血现在包括对FIXa活性的调节以及PS在TFPI/APC通路中的辅助因子活性。此外，PS对FIXa的直接抑制表明，PS，特别是PS的一种小衍生物，可用于治疗导致血栓并发症的PS缺乏或异常的个体。蛋白S （PS）是一种重要的天然抗凝剂。PS缺乏是获得性高凝的主要原因。获得性高凝导致数百万人的心肌梗死、中风和深静脉血栓。然而，尽管它在止血中的重要性，PS是最不了解的抗凝剂。即使在PS首次被描述40年后，我们仍在发现有关PS功能的信息。这篇综述的目的是强调最近的发现，促进我们对PS功能的理解，并解释由严重PS缺乏引起的高凝性。蛋白S一直被描述为活化蛋白C （APC）和组织因子途径抑制剂（TFPI）的辅助因子。然而，最近的一份报告描述了蛋白S对IXa因子（FIXa）的直接抑制作用，这是PS的一种完全被忽视的活性。血栓病正在成为一种越来越常见的疾病。遗传性PS缺乏症是一种抗凝血剂缺乏症，最终导致血栓形成。此外，PS缺乏是静脉血栓栓塞的易感因素，但PS缺乏对动脉血栓形成（如动脉缺血性中风）的影响尚不确定。孕妇血浆PS浓度降低。遗传性血栓是复发性流产的重要病因，抗凝治疗对仅有PS缺乏症的复发性流产妇女有益处。缺氧是静脉血栓栓塞（VTE）的危险因素，缺氧可下调血浆PS水平。重要的是，由于il6驱动的炎症反应对病毒感染造成肺损伤，COVID-19可导致低氧血症。由于缺氧降低了关键抗凝血剂PS的丰度，我们推测il6诱导的细胞因子爆炸结合低氧血症导致PS水平下降，从而加剧了COVID-19患者的血栓形成风险。
This review is intended to advance understanding of the anticoagulant function of an important plasma protein, Protein S. Despite 40+ years of research, we have not had a complete description of PS biology as it pertains to control of blood coagulation. However, the picture of PS function has become sharper with the recent discovery of FIXa inhibition by PS. Hemostasis mediated by PS now includes regulation of FIXa activity alongside the cofactor activities of PS in the TFPI/APC pathways. In addition, the direct inhibition of FIXa by PS suggests that PS, particularly a small derivative of PS, could be used to treat individuals with PS deficiencies or abnormalities that cause thrombotic complications. Protein S (PS) is an essential natural anticoagulant. PS deficiency is a major contributor to acquired hypercoagulability. Acquired hypercoagulability causes myocardial infarction, stroke, and deep vein thrombosis in millions of individuals. Yet, despite its importance in hemostasis, PS is the least understood anticoagulant. Even after 40 years since PS was first described, we are still uncovering information about how PS functions. The purpose of this review is to highlight recent findings that advance our understanding of the functions of PS and explain hypercoagulability caused by severe PS deficiency. Protein S has long been described as a cofactor for Activated Protein C (APC) and Tissue Factor Pathway Inhibitor (TFPI). However, a recent report describes direct inhibition of Factor IXa (FIXa) by Protein S, an activity of PS that had been completely overlooked. Thrombophilia is becoming a more frequently reported disorder. Hereditary PS deficiency is an anticoagulant deficiency that results eventually in thrombophilia. In addition, PS deficiency is a predisposing factor for venous thromboembolism, but an effect of PS deficiency in arterial thrombosis, such as arterial ischemic stroke, is uncertain. Plasma PS concentration decreases in pregnant women. Inherited thrombophilias are important etiologies for recurrent pregnancy loss, and anticoagulation therapy is of benefit to women with recurrent pregnancy loss who had documented only PS deficiency. Hypoxia is a risk factor for venous thromboembolism (VTE), and hypoxia downregulates plasma PS level. Importantly, COVID-19 can lead to hypoxemia because of lung damage from IL6-driven inflammatory responses to the viral infection. Because hypoxia decreases the abundance of the key anticoagulant PS, we surmise that the IL6-induced cytokine explosion combined with hypoxemia causes a drop in PS level that exacerbates the thrombotic risk in COVID-19 patients.
影响因子：
3.7
作者：
Naghavi S;Pourmohammadi A;Adibi I
通讯作者：
Adibi I