The Role of Fibrinolytic System in Health and Disease

Abstract

The fibrinolytic system is composed of the protease plasmin, its precursor plasminogen and their respective activators, tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), counteracted by their inhibitors, plasminogen activator inhibitor type 1 (PAI-1), plasminogen activator inhibitor type 2 (PAI-2), protein C inhibitor (PCI), thrombin activable fibrinolysis inhibitor (TAFI), protease nexin 1 (PN-1) and neuroserpin. The action of plasmin is counteracted by α2-antiplasmin, α2-macroglobulin, TAFI, and other serine protease inhibitors (antithrombin and α2-antitrypsin) and PN-1 (protease nexin 1). These components are essential regulators of many physiologic processes. They are also involved in the pathogenesis of many disorders. Recent advancements in our understanding of these processes enable the opportunity of drug development in treating many of these disorders.

Fibrinolytic system and COVID-19: From an innovative view of epithelial ion transport

“…Plasmin is the proteolytically active form of plasminogen, which can cleave fibrin to degradation products, and is upregulated or downregulated by tissue plasminogen activator/urokinase plasminogen activator (tPA/uPA) or PAI-1, respectively [44] , [45] , [46] . Remarkable postmortem findings present that SARS-CoV-2 infection can give rise to diffuse alveolar damage and thromboembolism [47] .…”

Dysregulated fibrinolysis and plasmin activation promote the pathogenesis of osteoarthritis

“…The fibrinolytic system, along with coagulation, is tightly regulated by multiple inhibitors, cofactors, and receptors to ensure balanced hemostasis. For example, circulating plasmin is neutralized by α2-macroglobulin (12) and antiplasmin (13,14) whereas tPA is blocked from activation by serine protease inhibitors (serpins), such as plasminogen activator inhibitor-1 (PAI-1), and nonserpin inhibitors (15).…”

Plant-Derived Compounds and Extracts as Modulators of Plasmin Activity—A Review

“…However, removal of fibrin clots is only a part of pleiotropic activity, both of plasmin itself and other fibrinolytic proteins. Functions of the fibrinolytic system extend beyond blood physiology and vascular hemostasis and include participation in extracellular matrix (ECM) degradation, tissue remodeling, wound healing, immune response, and other physiological and pathological processes [ 1 , 2 , 3 ] ( Figure 1 ). Besides degradation of fibrinogen and fibrin, plasmin hydrolyzes many other protein substrates, including blood coagulation factors (V, VIII, IX, X, von Willebrand factor, FXII, and pre-kallikrein), vascular endothelial growth factor, C3 and C5 complement components, protease-activated receptor-1 (PAR-1), matrix metalloproteinase zymogenes (proMMPs), as well as ECM proteins, e.g., fibronectin, tenascin, collagen, and laminin [ 4 ].…”