Thrombotic risk markers: tissue plasminogen activator-inhibitor complex/ tissue plasminogen activator inhibitor-1 (part 2)
https://doi.org/10.24884/2078-5658-2026-23-1-110-117
Abstract
The fibrinolysis system is one of the most important regulators of homeostasis and participates in maintaining stable blood flow. The key element of this system is the balance of plasminogen activators and inhibitors, which can be considered as markers of normal physiological and pathological reactions. The use of laboratory determination of the level of the tissue plasminogen activator/tissue plasminogen activator inhibitor-1 (t-PA/PAI-1) complex in clinical practice is promising in diagnostic and prognostic terms as a biomarker of increased thrombotic risk in the early stages of the development of complications of the disease. This review will provide up-to-date information on practical applications, and diagnostic capabilities, and using such a marker of thrombotic risk as the t-PA/PAI-1 complex in neurological and cardiovascular diseases, obstetric pathology, in patients with COVID-19, as well as in metabolic disorders and in general conditions associated with damage to endothelial cells and an imbalance of the fibrinolytic system.
About the Authors
M. M. Tanashyan
Russian Center of Neurology and Neurosciences
Russian Federation
Russian Federation
Tanashyan Marine M., Dr. of Sci. (Med.), Professor, Academician of the RAS, Deputy Director for Academic Affairs, Head of the 1st Neurological Department, Institute of Clinical and Preventive Neurology
Scopus Author ID: 6506228066
WoS ResearcherID: F-8483-2014
80, Volokolamskoe shosse, Moscow, 125367
E. V. Roitman
Russian Center of Neurology and Neurosciences; Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Roitman Eugene V., Dr. of Sci. (Biol.), Leading Research Fellow; Professor, Department of Oncology, Hematology and Radiation Therapy
Scopus Author ID: 7004167632
WoS ResearcherID: M-6541-2017
80, Volokolamskoe shosse, Moscow, 125367
1, Ostrovityanova str., Moscow, 117513
A. A. Raskurazhev
Russian Center of Neurology and Neurosciences
Russian Federation
Russian Federation
Raskurazhev Anton A., Cand. of Sci. (Med.), Neurologist, Senior Research Fellow of the 1st Neurological Department, Institute of Clinical and Preventive Neurology
80, Volokolamskoe shosse, Moscow, 125367
P. I. Kuznetsova
Russian Center of Neurology and Neurosciences
Russian Federation
Russian Federation
Kuznetsova Polina I., Cand. of Sci. (Med.), Research Fellow of the 1st Neurological Department, Institute of Clinical and Preventive Neurology
80, Volokolamskoe shosse, Moscow, 125367
A. S. Mazur
Russian Center of Neurology and Neurosciences
Russian Federation
Russian Federation
Mazur Andrey S., Postgraduate Student of the 1st Neurological Department, Institute of Clinical and Preventive Neurology
80, Volokolamskoe shosse, Moscow, 125367
References
1. Borodkina A. V., Deryabin P. I., Griukova A. A., Nikolsky N. N. “Social life” of senescent cells: what is SASP and why study it? Acta Naturae, 2018, no. 1, pp. 4–15. (In Russ.).
2. Kalinin R. E., Klimentova E. A., Suchkov I. A. et al. The effect of the fibrinolysis system on the outcomes of thrombolytic therapy in acute vascular pathology. Neotlozhnaja medicinskaja pomoshh’. Zhurnal imeni N. V. Sklifosovskogo, 2024, vol. 13, no. 4, pp. 631–640. (In Russ.). http://doi.org/10.23934/2223-9022-2024-13-4-631-640.
3. Mikheev R. K., Andreeva E. N., Grigoryan O. R. et al. Molecular and cellular mechanisms of ageing: modern knowledge (literature review). Problemy Endokrinologii, 2023, vol. 69, no. 5, pp. 45–54. (In Russ.). http://doi.org/10.14341/probl13278.
4. Nikolaeva M. G., Serdiuk G. V., Gorbacheva T. I. et al. Relationship between preeclampsia and SERPINE1 (PAI-1-675 G4/G5) gene polymorphism. Systematic review. A metaanalysis. Problemy reprodukcii, 2016, vol. 22, no. 4, pp. 115–122. (In Russ.). http://doi.org/10.17116/repro2016224115-122.
5. Tanashyan M. M., Antonova K. V., Lagoda O. V. et al. Obesity and prothrombotic state in patients with cerebrovascular diseases. Tromboz, gemostaz i reologija, 2023, no. 3, pp. 53–62. (In Russ.). http://doi.org10.25555/THR.2023.3.1069.
6. Angelucci F., Veverova K., Katonová A. et al. Plasminogen activator inhibitor-1 serum levels in frontotemporal lobar degeneration // J Cell Mol Med. – 2024. – Vol. 28, № 5. – e18013. http://doi.org/10.1111/jcmm.18013.
7. Chen R., Yan J., Liu P. et al. Plasminogen activator inhibitor links obesity and thrombotic cerebrovascular diseases: The roles of PAI-1 and obesity on stroke // Metab Brain Dis. – 2017. – Vol. 32, № 3. – P. 667–673. http://doi.org/10.1007/s11011-017-0007-3.
8. Dobrynina L. A., Shabalina A. A., Zabitova M. R. et al. Tissue plasminogen activator and MRI signs of cerebral small vessel disease // Brain Sci. – 2019. – Vol. 9, № 10. – P. 266. http://doi.org/10.3390/brainsci9100266.
9. Dungan G. D., Kantarcioglu B., Odeh A. et al. Vascular endothelial dysfunction and immunothrombosis in the pathogenesis of atrial fibrillation // Clin Appl Thromb Hemost. – 2024. – Vol. 30. – 10760296241296138. http://doi.org/10.1177/10760296241296138.
10. Feng Y. F., Su M. Y., Xu H. X. et al. Plasma tissue plasminogen activator-inhibitor complex levels in acute myocardial infarction patients: an observational study // BMC Cardiovasc Disord. – 2024. – Vol. 24, № 1. – P. 722. http://doi.org/10.1186/s12872-024-04406-9.
11. Girard R. A., Chauhan P. S., Tucker T. A. et al. Increased expression of plasminogen activator inhibitor-1 (PAI-1) is associated with depression and depressive phenotype in C57Bl/6J mice // Exp Brain Res. – 2019. – Vol. 237, № 12. – P. 3419–3430. http://doi.org/10.1007/s00221-019-05682-0.
12. Ishii A., Yamada S., Yamada R. et al. t-PA activity in peripheral blood obtained from pregnant women // J Perinat Med. – 1994. – Vol. 22, № 2. – P. 113–117. http://doi.org/10.1515/jpme.1994.22.2.113.
13. Jin X., Duan Y., Bao T. et al. The values of coagulation function in COVID-19 patients // PLoS One. – 2020. – Vol. 15, № 10. – e0241329. http://doi.org/10.1371/journal.pone.0241329.
14. Jung R. G., Motazedian P., Ramirez F. D. et al. Association between plasminogen activator inhibitor-1 and cardiovascular events: a systematic review and meta-analysis // Thromb J. – 2018. – Vol. 16. – P. 12. http://doi.org/10.1186/s12959-018-0166-4.
15. Kanno Y. The roles of fibrinolytic factors in bone destruction caused by inflammation // Cells. – 2024. – Vol. 13, № 6. – P. 516. http://doi.org/10.3390/cells13060516.
16. Kudryashova T. V., Zaitsev S. V., Jiang L. et al. PAI-1 deficiency drives pulmonary vascular smooth muscle remodeling and pulmonary hypertension // Am J Physiol Lung Cell Mol Physiol. – 2024. – Vol. 327, № 3. – L319–L326. http://doi.org/10.1152/ajplung.00110.2024.
17. Lee T. W., Tsang V. W., Birch N. P. Physiological and pathological roles of tissue plasminogen activator and its inhibitor neuroserpin in the nervous system // Front Cell Neurosci. – 2015. – Vol. 9. – P. 396. http://doi.org/10.3389/fn-cel.2015.00396.
18. Lehikoinen J., Strandin T., Parantainen J. et al. Fibrinolysis associated proteins and lipopolysaccharide bioactivity in plasma and cerebrospinal fluid in multiple sclerosis // J Neuroimmunol. – 2024. – Vol. 395. – P. 578432. http://doi.org/10.1016/j.jneuroim.2024.578432.
19. Levine J. A., Oleaga C., Eren M. et al. Role of PAI-1 in hepatic steatosis and dyslipidemia // Sci Rep. – 2021. – Vol. 11, № 1. – P. 430. http://doi.org/10.1038/s41598-020-79948-x.
20. Liao C., Liu G., Li L. et al. Predictive value of thrombin-antithrombin III complex and tissue plasminogen activator-inhibitor complex biomarkers in assessing the severity of early-stage acute pancreatitis // J Gastroenterol Hepatol. – 2024. – Vol. 39, № 10. – P. 2088–2096. http://doi.org/10.1111/jgh.16641.
21. Liu Z., Liu C., Zhong M. et al. Changes in coagulation and fibrinolysis in post-cesarean section parturients treated with low molecular weight heparin // Clin Appl Thromb Hemost. – 2020. – Vol. 26. – 1076029620978809. http://doi.org/10.1177/1076029620978809.
22. Marchetti M., Gomez-Rosas P., Russo L. et al. Fibrinolytic proteins and factor XIII as predictors of thrombotic and hemorrhagic complications in hospitalized COVID-19 patients // Front Cardiovasc Med. – 2022. – Vol. 9. – 96362. http://doi.org/10.3389/fcvm.2022.896362.
23. Meltzer M. E., Lisman T., de Groot P. G. et al. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1 // Blood. – 2010. – Vol. 116, № 1. – P. 113–121. http://doi.org/10.1182/blood-2010-02-267740.
24. Nordenhem A., Leander K., Hallqvist J. et al. The complex between tPA and PAI-1: risk factor for myocardial infarction as studied in the SHEEP project // Thromb Res. – 2005. – Vol. 116, № 3. – P. 223–232. http://doi.org/10.1016/j.thromres.2004.12.007.
25. van Overbeek E. C., Staals J., Knottnerus I. L. et al. Plasma tPA-activity and progression of cerebral white matter hyperintensities in lacunar stroke patients // PLoS One. – 2016. – Vol. 11, № 3. – e0150740. http://doi.org/10.1371/journal.pone.0150740.
26. Paganelli F., Alessi M. C., Morange P. et al. Relationship of plasminogen activator inhibitor-1 levels following thrombolytic therapy with rt-PA as compared to streptokinase and patency of infarct related coronary artery // Thromb Haemost. – 1999. – Vol. 82, № 1. – P. 104–108.
27. Schramm T., Rast J., Mehic D. et al. Fibrinolysis is impaired in patients with primary immune thrombocytopenia // J Thromb Haemost. – 2024. – Vol. 22, № 11. – P. 3209–3220. http://doi.org/10.1016/j.jtha.2024.07.034.
28. Shahid S., Saeed H., Iqbal M. et al. Comparative efficacy and safety of tissue plasminogen activators (tPA) in acute ischemic stroke: A systematic review and network meta-analysis of randomized controlled trials // J Stroke Cerebrovasc Dis. – 2025. – Vol. 34, № 3. – 108230. http://doi.org/10.1016/j.jstrokecerebrovasdis.2025.108230.
29. Sillen M., Declerck P. J. A Narrative review on plasminogen activator inhibitor-1 and its (patho)physiological role: to target or not to target? // Int J Mol Sci. – 2021. – Vol. 22, № 5. – 2721. http://doi.org/10.3390/ijms22052721.
30. Somodi S., Seres I., Lőrincz H. et al. Plasminogen activator inhibitor-1 level correlates with lipoprotein subfractions in obese nondiabetic subjects // Int J Endocrinol. – 2018. – Vol. 2018. – 9596054. http://doi.org/10.1155/2018/9596054.
31. Song C., Burgess S., Eicher J. D. et al. Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease // J Am Heart Assoc. – 2017. – Vol. 6, № 6. – e004918. http://doi.org/10.1161/JAHA.116.004918.
32. Sun Q., Lu Y., Zhong J. et al. A retrospective case-control study on the diagnostic values of hemostatic markers in hypertensive disorder of pregnancy // Lab Med. – 2023. – Vol. 54, № 4. – P. 392-399. http://doi.org/10.1093/labmed/lmac128.
33. Tofler G. H., Massaro J., O’Donnell C. J. et al. Plasminogen activator inhibitor and the risk of cardiovascular disease: The Framingham Heart Study // Thromb Res. – 2016. – Vol. 140. – P. 30–35. http://doi.org/10.1016/j.thromres.2016.02.002.
34. Toomer K. H., Gerber G. F., Zhang Y. et al. SARS-CoV-2 infection results in upregulation of Plasminogen Activator Inhibitor-1 and Neuroserpin in the lungs, and an increase in fibrinolysis inhibitors associated with disease severity // EJHaem. – 2023. – Vol. 4, № 2. – P. 324–338. http://doi.org/10.1002/jha2.654.
35. Wang L., Zhong J., Xiao D. et al. Thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2-plasmininhibitor complex (PIC), and tissue plasminogen activator-inhibitor complex (t-PAIC) assessment of fibrinolytic activity in postpartum hemorrhage: a retrospective comparative cohort study // Ann Transl Med. – 2022. – Vol. 10, № 23. – P. 1273. http://doi.org/10.21037/atm-22-5221.
36. Winter M.-P., Kleber M. E., Koller L. et al. Prognostic significance of tPA/PAI-1 complex in patients with heart failure and preserved ejection fraction // Thromb Haemost. – 2017. – Vol. 117, № 3. – P. 471–478. http://doi.org/10.1160/TH16-08-0600.
37. Yang Z., Gao C., Li Z. et al. The changes of tPA/PAI-1 system are associated with the ratio of BDNF/proBDNF in major depressive disorder and SSRIs antidepressant treatment // Neuroscience. – 2024. – Vol. 559. – P. 220–228. http://doi.org/10.1016/j.neuroscience.2024.09.005.
38. Yarmolinsky J., Bordin Barbieri N., Weinmann T. et al. Plasminogen activator inhibitor-1 and type 2 diabetes: a systematic review and meta-analysis of observational studies // Sci Rep. 2016. – Vol. 6. – P. 17714. http://doi.org/10.1038/srep17714.
39. Yip H.-K., Yuen C.-M., Chen K.-H. et al. Tissue plasminogen activator deficiency preserves neurological function and protects against murine acute ischemic stroke // Int J Cardiol. – 2016. – Vol. 205. – P. 133–141. http://doi.org/10.1016/j.ijcard.2015.11.168.
40. Zhao X., Yang S., Lei R. et al. Value of novel thrombotic markers for predicting occurrence of the malignant cerebral artery infarction: a prospective clinical study // Front Neurol. – 2023. – Vol. 14. – 1238742. http://doi.org/10.3389/fneur.2023.1238742.
41. Zipperle J., Ziegler B., Schöchl H. et al. Conventional and pro-inflammatory pathways of fibrinolytic activation in non-traumatic hyperfibrinolysis // J Clin Med. – 2022. – Vol. 11, № 24. – 7305. http://doi.org/10.3390/jcm11247305.
Review
For citations:
Tanashyan M.M., Roitman E.V., Raskurazhev A.A., Kuznetsova P.I., Mazur A.S. Thrombotic risk markers: tissue plasminogen activator-inhibitor complex/ tissue plasminogen activator inhibitor-1 (part 2). Messenger of ANESTHESIOLOGY AND RESUSCITATION. 2026;23(1):110-117. (In Russ.) https://doi.org/10.24884/2078-5658-2026-23-1-110-117
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