Napolitano Filomena, Montuori Nunzia
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80135 Naples, Italy.
J Clin Med. 2021 Feb 1;10(3):518. doi: 10.3390/jcm10030518.
The main physiological functions of plasmin, the active form of its proenzyme plasminogen, are blood clot fibrinolysis and restoration of normal blood flow. The plasminogen activation (PA) system includes urokinase-type plasminogen activator (uPA), tissue-type PA (tPA), and two types of plasminogen activator inhibitors (PAI-1 and PAI-2). In addition to the regulation of fibrinolysis, the PA system plays an important role in other biological processes, which include degradation of extracellular matrix such as embryogenesis, cell migration, tissue remodeling, wound healing, angiogenesis, inflammation, and immune response. Recently, the link between PA system and angioedema has been a subject of scientific debate. Angioedema is defined as localized and self-limiting edema of subcutaneous and submucosal tissues, mediated by bradykinin and mast cell mediators. Different forms of angioedema are linked to uncontrolled activation of coagulation and fibrinolysis systems. Moreover, plasmin itself can induce a potentiation of bradykinin production with consequent swelling episodes. The number of studies investigating the PA system involvement in angioedema has grown in recent years, highlighting its relevance in etiopathogenesis. In this review, we present the components and diverse functions of the PA system in physiology and its importance in angioedema pathogenesis.
纤溶酶是其酶原纤溶酶原的活性形式，其主要生理功能是溶解血凝块并恢复正常血流。纤溶酶原激活（PA）系统包括尿激酶型纤溶酶原激活剂（uPA）、组织型PA（tPA）以及两种类型的纤溶酶原激活剂抑制剂（PAI-1和PAI-2）。除了调节纤维蛋白溶解外，PA系统在其他生物学过程中也发挥着重要作用，这些过程包括细胞外基质的降解，如胚胎发生、细胞迁移、组织重塑、伤口愈合、血管生成、炎症和免疫反应。最近，PA系统与血管性水肿之间的联系一直是科学争论的主题。血管性水肿被定义为皮下和粘膜下组织的局限性自限性水肿，由缓激肽和肥大细胞介质介导。不同形式的血管性水肿与凝血和纤维蛋白溶解系统的失控激活有关。此外，纤溶酶本身可诱导缓激肽生成增强，继而引发肿胀发作。近年来，研究PA系统与血管性水肿关系的研究数量不断增加，突出了其在发病机制中的相关性。在本综述中，我们介绍了PA系统在生理学中的组成部分和多种功能及其在血管性水肿发病机制中的重要性。
