Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
Semin Thromb Hemost. 2023 Apr;49(3):305-313. doi: 10.1055/s-0042-1758791. Epub 2022 Dec 15.
Plasminogen activator inhibitor 1 (PAI-1), a SERPIN inhibitor, is primarily known for its regulation of fibrinolysis. However, it is now known that this inhibitor functions and contributes to many (patho)physiological processes including inflammation, wound healing, cell adhesion, and tumor progression.This review discusses the past, present, and future roles of PAI-1, with a particular focus on the discovery of this inhibitor in the 1970s and subsequent characterization in health and disease. Throughout the past few decades diverse functions of this serpin have unraveled and it is now considered an important player in many disease processes. PAI-1 is expressed by numerous cell types, including megakaryocytes and platelets, adipocytes, endothelial cells, hepatocytes, and smooth muscle cells. In the circulation PAI-1 exists in two pools, within plasma itself and in platelet α-granules. Platelet PAI-1 is secreted following activation with retention of the inhibitor on the activated platelet membrane. Furthermore, these anucleate cells contain PAI-1 messenger ribonucleic acid to allow de novo synthesis.Outside of the traditional role of PAI-1 in fibrinolysis, this serpin has also been identified to play important roles in metabolic syndrome, obesity, diabetes, and most recently, acute respiratory distress syndrome, including coronavirus disease 2019 disease. This review highlights the complexity of PAI-1 and the requirement to ascertain a better understanding on how this complex serpin functions in (patho)physiological processes.
纤溶酶原激活物抑制剂 1（PAI-1），一种丝氨酸蛋白酶抑制剂，主要因其对纤维蛋白溶解的调节作用而被人们所熟知。然而，目前已知该抑制剂还具有许多（病理）生理功能，包括炎症、伤口愈合、细胞黏附和肿瘤进展等。本文回顾了 PAI-1 的过去、现在和未来的作用，特别关注了该抑制剂在 20 世纪 70 年代的发现以及随后在健康和疾病中的特征。在过去的几十年中，这种丝氨酸蛋白酶抑制剂的多种功能逐渐被揭示出来，目前它被认为是许多疾病过程中的重要参与者。PAI-1 由多种细胞类型表达，包括巨核细胞和血小板、脂肪细胞、内皮细胞、肝细胞和平滑肌细胞。在循环中，PAI-1 存在于两个池内，即血浆本身和血小板α-颗粒中。血小板 PAI-1 在被激活后释放出来，同时抑制剂被保留在激活的血小板膜上。此外，这些无核细胞含有 PAI-1 信使核糖核酸，以允许从头合成。除了 PAI-1 在纤维蛋白溶解中的传统作用外，该丝氨酸蛋白酶抑制剂还被确定在代谢综合征、肥胖症、糖尿病以及最近的急性呼吸窘迫综合征（包括 2019 年冠状病毒病）中发挥重要作用。本文强调了 PAI-1 的复杂性，需要更好地了解这种复杂的丝氨酸蛋白酶抑制剂在（病理）生理过程中的作用机制。
