The role of the coagulation-fibrinolysis system in airway and lung remodeling.

Abstract

The coagulation and fibrinolytic systems are distinct biological processes yet intricately interconnected through various regulatory mechanisms. The coagulation cascade not only serves to prevent blood loss from damaged vessels but also acts as a defense mechanism against invading pathogens and initiates vascular repair. This physiological response culminates in the formation of a fibrin mesh through a well-orchestrated cascade of enzymatic reactions. Conversely, the fibrinolytic system functions to dissolve thrombi formed by the coagulation system. Its principal effector, plasmin, degrades the fibrin network and activates a range of bioactive molecules involved in diverse physiological responses. The coagulation and fibrinolytic pathways and associated inflammatory and wound-healing processes are tightly regulated and mutually influential. Airway and pulmonary remodeling typically refer to pathological alterations in lung tissue, including inflammation, fibrosis, emphysema, and alveolar damage. These changes can be driven by chronic disease, acute inflammation, or environmental factors. Significantly, a localized procoagulant state or dysfunction in the fibrinolytic system within the respiratory tract may contribute to these remodeling processes, ultimately impairing respiratory function and leading to significant health consequences. Despite the promising effects of conventional anticoagulant therapies in animal models, clinical translation in humans has often failed to yield clear therapeutic benefits. This discrepancy is likely attributable to the inherent complexity and dual roles of the coagulation-fibrinolysis axis and the persistent risk of bleeding associated with systemic anticoagulation. Therefore, continued investigation into the underlying mechanisms and the development of novel, targeted anticoagulant strategies are warranted to achieve effective and safe therapeutic outcomes.