Plasminogen System: A Versatile Regulator of Fibrinolysis, Inflammation, and Tissue Remodeling in Health and Disease

The plasminogen system is a fundamental proteolytic cascade, essential for maintaining physiological homeostasis across numerous biological processes. Beyond its well-known role in fibrinolysis (dissolving blood clots), it critically regulates inflammation, wound healing, and tissue remodeling. Dysregulation of this system contributes significantly to a range of pathologies, including hereditary disorders, tumor dissemination, bacterial invasion, and viral priming. Current therapeutic approaches often target specific components, but a holistic understanding of its multifaceted nature is crucial for developing more effective and targeted interventions.

This comprehensive review synthesizes decades of research with recent advances on the plasminogen system. The authors explored its evolutionary trajectory, detailed structural aspects of its components, elucidated various activation mechanisms, and mapped its intricate regulatory pathways. Furthermore, the review examined the current landscape of pharmacological modulation strategies targeting the system. The primary objective was to highlight the plasminogen system's multifaceted nature—serving as both a guardian of physiological balance and a potential driver of disease—and to discuss its components as promising therapeutic targets and tools.

The plasminogen system is identified as a central proteolytic system crucial for maintaining homeostasis through its regulation of diverse physiological pathways including fibrinolysis, inflammation, wound healing, and tissue remodelling. Beyond its direct proteolytic actions, the system functions as a critical hub for crosstalk with other biological systems, integrating various signals to ensure physiological balance. However, its dysregulation, misuse, or hijacking by pathogens is a significant driver of various pathologies, such as hereditary disorders, tumour dissemination, bacterial invasion, and viral priming. The review details the system's complex evolution, structural characteristics, and intricate activation and regulatory mechanisms, emphasizing its adaptability and integral role across species. Pharmacological modulation strategies are explored, showcasing how targeting specific components can influence disease progression.

The plasminogen system's components are highlighted as promising therapeutic targets and tools, offering avenues for pharmacological modulation to address diseases where its balance is disrupted.