SUMMARY
Venous thrombosis is a very common and financially challenging disease. Deep vein thrombosis can cause permanent damage to the venous system and lead to swelling, ulcers, gangrene and other symptoms in the affected organ. In addition, more than half of pulmonary embolisms are caused by venous thrombosis, which is the most serious cause of death in patients with ischemic heart disease and stroke. It seems that deep vein thrombosis has become a serious disease affecting human health. In recent years, an increasing number of studies have led to the belief that inflammatory responses cause venous thrombosis. Here, the transcription factor NF-κb is a central mediator of inflammation and the NF-κb signaling pathway may regulate the proinflammatory and coagulation response. Therefore, investigating and exploiting this mechanism may help to find a new solution for the prevention and treatment of thrombosis.
Keywords: Thrombosis, NF-κB signaling pathway, inflammation, TNF-α, IL-6, transcription factor, VCAM

---

REFERENCES

1. Áinle F.N., Kevane B. Which patients are at high risk of recurrent venous thromboembolism (deep vein thrombosis and pulmonary embolism)? // Blood advances, 2020. 4(21), 5595-5606.
2. Anderson J.A., Weitz J.I. Hypercoagulable states Critical care clinics, 2011. 27(4), 933-952.
3. Blann A.D., Lip G.Y. Virchow's triad revisited: the importance of soluble coagulation factors, the endothelium, and platelets // Thrombosis research, 2001. 101(4), 321-327.
4. Cines D.B., Pollak E.S., Buck C.A., Loscalzo J., Zimmerman G.A., McEver R., Stern D.M. Endothelial cells in physiology and in the pathophysiology of vascular disorders // Blood, The Journal of the American Society of Hematology, 1998;91(10), 3527-3561.
5. Chan N., Eikelboom J. Hypercoagulability and thrombosis in COVID-19: a modifiable cause for mortality? // European Heart Journal, 2021; 42(33), 3143-3145.
6. Chang M., Guo F., Zhou Z. et al. HBP induces the expression of monocyte chemoattractant protein-1 via the FAK/PI3K/AKT and p38 MAPK/NF-κB pathways in vascular endothelial cells // Cellular signalling, 2018. 43, 85-94.
7. Chien S., Li S., Shyy J. Y. Effects of mechanical forces on signal transduction and gene expression in endothelial cells // Hypertension, 1998. 31(1), 162-169.
8. Davies P.F. Flow-mediated endothelial mechanotransduction // Physiological reviews, 1995.75(3), 519-560.
9. Deshmane S.L., Kremlev S., Amini S., Sawaya B.E. Monocyte chemoattractant protein-1 (MCP-1): an overview // Journal of interferon and cytokine research, 2009. 29(6), 313-326.
10. Di Nisio M., van Es N., Büller H.R. Deep vein thrombosis and pulmonary embolism // The Lancet, 2016. 388(10063), 3060-3073.
11. Ding P., Zhang S., Yu M., Feng Y. et al. IL-17A promotes the formation of deep vein thrombosis in a mouse model // International Immunopharmacology, 2018. 57, 132-138.
12. Gilmore T.D. Introduction to NF-κB: players, pathways, perspectives // Oncogene, 2006. 25(51), 6680-6684.
13. Gimbrone Jr M.A., García-Cardeña G. Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis // Cardiovascular Pathology, 2013. 22(1), 9-15.
14. Ghosh S., Hayden M.S. New regulators of NF-κB in inflammation // Nature Reviews Immunology, 2008. 8(11), 837-848.
15. Gupta S.C., Kim J.H., Prasad S., Aggarwal B.B. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals // Cancer and Metastasis Reviews, 2010. 29, 405-434.
16. Gupta S.C., Sundaram C., Reuter S., Aggarwal B.B. Inhibiting NF-κB activation by small molecules as a therapeutic strategy // Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 2010; 1799(10-12), 775-787.
17. Hayden M.S., Ghosh S. Shared principles in NF-κB signaling // Cell, 2008; 132(3), 344-362.
18. Iba T., Helms J., Levi M., Levy J. H. Thromboinflammation in acute injury: infections, heatstroke, and trauma // Journal of Thrombosis and Haemostasis, 2024. 22(1), 7-22.
19. Kong D.H., Kim Y.K., Kim M.R., Jang J.H., Lee S. Emerging roles of vascular cell adhesion molecule-1 (VCAM-1) in immunological disorders and cancer // International journal of molecular sciences, 2018. 19(4), 1057.
20. Lehoux S., Tedgui A. Cellular mechanics and gene expression in blood vessels // Journal of biomechanics, 2003. 36(5), 631-643.
21. Margetic S. Inflammation and hemostasis // Biochemia medica, 2012;22(1), 49-62.
22. Mussbacher M., Salzmann M., Brostjan C., Hoesel, B., Schoergenhofer C., Datler H., Schmid, J.A. Cell type-specific roles of NF-κB linking inflammation and thrombosis // Frontiers in immunology, 2019. 10, 85.
23. Nigro P., Abe J. I., Berk B. C. Flow shear stress and atherosclerosis: a matter of site specificity // Antioxidants and redox signaling, 2011. 15(5), 1405-1414.
24. Piazza G. Thrombophilia and Hypercoagulability // Circulation, 2014. 130(2), e9-e10.
25. Pilard M., Ollivier E.L., Gourdou-Latyszenok V. et al. Endothelial cell phenotype, a major determinant of venous thrombo-inflammation // Frontiers in Cardiovascular Medicine, 2022; 9, 864735.
26. Resnick N., Yahav H., Shay-Salit A. et al. Fluid shear stress and the vascular endothelium: for better and for worse // Progress in biophysics and molecular biology, 2003. 81(3), 177-199.
27. Salomon O., Steinberg D.M., Zivelin A., Gitel S., Dardik R., Rosenberg N., Seligsohn U. Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism: prevalence and risk assessment // Arteriosclerosis, thrombosis, and vascular biology, 1999. 19(3), 511-518.
28. Stakos D.A., Kambas K., Konstantinidis T., Mitroulis I. et al. Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction // European heart journal, 2015, 36(22), 1405-1414.
29. Sun S.C. The non-canonical NF-κB pathway in immunity and inflammation // Nature reviews immunology, 2017. 17(9), 545-558.
30. Thålin C., Hisada Y., Lundström S., Mackman N., Wallén H. Neutrophil extracellular traps: villains and targets in arterial, venous, and cancer-associated thrombosis // Arteriosclerosis, thrombosis, and vascular biology, 2019. 39(9), 1724-1738.
31. Urban C.F., Ermert D., Schmid M., Abu-Abed U., Goosmann C., Nacken W., Zychlinsky A. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans // PLoS pathogens, 2009. 5(10), e1000639.
32. Vallabhapurapu S., Karin M. Regulation and function of NF-κB transcription factors in the immune system // Annual review of immunology, 2009. 27(1), 693-733.
33. Vandenbroucke J.P., Koster T., Rosendaal F.R. et al. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation // The Lancet,1994. 344(8935), 1453-1457.
34. Verhamme P., Hoylaerts M.F. The pivotal role of the endothelium in hemostasis and thrombosis // Acta Clinica Belgica, 2006. 61(5), 213-219.
35. Xiao G., Harhaj E.W., Sun S.C. NF-κB-inducing kinase regulates the processing of NF-κB2 p100 // Molecular cell, 2001. 7(2), 401-409.
36. Xu X.R., Zhang D., Oswald B.E. et al. Platelets are versatile cells: New discoveries in hemostasis, thrombosis, immune responses, tumor metastasis and beyond // Critical reviews in clinical laboratory sciences, 2016. 53(6), 409-430.
37. Yau J.W., Teoh H., Verma S. Endothelial cell control of thrombosis // BMC cardiovascular disorders, 2015. 15, 1-11.