A. O. Tykhomyrov*, O. I. Yusova, L. G. Kapustianenko, I. I. Patalakh,
T. A. Yatsenko, V. L. Bilous, T. V. Grynenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine,
Department of Enzyme Chemistry and Biochemistry, Kyiv;
*e-mail: artem_tykhomyrov@ukr.net

Received: 20 April 2025; Revised: 02 June 2025;
Accepted: 30 October 2025; Available on-line: 2025

The plasminogen/plasmin (Pg/Pm) system is a cornerstone of various biological processes, encompassing roles in fibrinolysis, angiogenesis, inflammation, wound healing, and tumor biology. This review consolidates knowledge on the multifaceted functions of the Pg/Pm system proteins in health and disease, highlighting historical developments, recent advancements, and the contributions of the Department of Enzyme Chemistry and Biochemistry to the understanding of their molecular mechanisms of function. We have explored the regulation of fibrinolysis and its intricate interplay with proteins of the Pg/Pm system, delving into their pivotal role in hemostatic balance. Reciprocal interactions between Pg/Pm system proteins and platelets underscore their contribution to thrombosis, fibrinolysis, inflammation, and vascular remodeling. In oncology, Pg/Pm system proteins orchestrate tumor growth and metastasis through their involvement in extracellular matrix remodeling, angiogenesis, and cancer cell survival. However, angiostatins – proteolyti­cally-derived fragments of Pg/Pm – emerge as multifunctional polypeptides, which are known to affect cell migration, angiogenesis, and inflammation, suppress tumor growth and metastasis. Contribution of Pg/Pm to reparative processes, including wound healing, further emphasizes their therapeutic potential in regenerative medicine. Moreover, these proteins play crucial roles in ocular health, where their dysregulation may lead to the pathogenesis of ophthalmic diseases. In conclusion, advancement of our understanding of this versatile system functions through continued research is pivotal for applications of these proteins as diagnostic and prognostic biomarkers for cardiovascular disorders, inflammatory pathologies, cancer, autoimmune conditions, and various diabetic complications, offering insights into early detection of disease and development of innovative therapeutic strategies, ultimately driving progress in personalized medicine.