Department of Cardiac Thoracic Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, 1090 Vienna, Austria.
Division of General and Surgical Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Int J Mol Sci. 2021 Apr 20;22(8):4283. doi: 10.3390/ijms22084283.
Antithrombin (AT) is a natural anticoagulant that interacts with activated proteases of the coagulation system and with heparan sulfate proteoglycans (HSPG) on the surface of cells. The protein, which is synthesized in the liver, is also essential to confer the effects of therapeutic heparin. However, AT levels drop in systemic inflammatory diseases. The reason for this decline is consumption by the coagulation system but also by immunological processes. Aside from the primarily known anticoagulant effects, AT elicits distinct anti-inflammatory signaling responses. It binds to structures of the glycocalyx (syndecan-4) and further modulates the inflammatory response of endothelial cells and leukocytes by interacting with surface receptors. Additionally, AT exerts direct antimicrobial effects: depending on AT glycosylation it can bind to and perforate bacterial cell walls. Peptide fragments derived from proteolytic degradation of AT exert antibacterial properties. Despite these promising characteristics, therapeutic supplementation in inflammatory conditions has not proven to be effective in randomized control trials. Nevertheless, new insights provided by subgroup analyses and retrospective trials suggest that a recommendation be made to identify the patient population that would benefit most from AT substitution. Recent experiment findings place the role of various AT isoforms in the spotlight. This review provides an overview of new insights into a supposedly well-known molecule.
抗凝血酶 (AT) 是一种天然抗凝剂，可与凝血系统的激活蛋白酶以及细胞表面的肝素硫酸蛋白聚糖 (HSPG) 相互作用。这种在肝脏中合成的蛋白质对于赋予治疗性肝素的作用也很重要。然而，在全身性炎症性疾病中，AT 水平会下降。这种下降的原因是凝血系统的消耗，也与免疫过程有关。除了主要已知的抗凝作用外，AT 还引发独特的抗炎信号反应。它与糖萼的结构（连接蛋白-4）结合，并通过与表面受体相互作用进一步调节内皮细胞和白细胞的炎症反应。此外，AT 还具有直接的抗菌作用：根据 AT 的糖基化情况，它可以与细菌细胞壁结合并穿孔。来自 AT 蛋白水解降解的肽片段具有抗菌特性。尽管具有这些有前景的特性，但在随机对照试验中，在炎症情况下进行治疗性补充并未被证明有效。然而，亚组分析和回顾性试验提供的新见解表明，应建议确定最受益于 AT 替代的患者人群。最近的实验结果将各种 AT 同工型的作用置于聚光灯下。这篇综述提供了对一种据称众所周知的分子的新见解概述。
