The role of P-selectin in pulmonary thromboembolism
DOI:
https://doi.org/10.52692/1857-0011.2025.1-81.17Keywords:
P-selectin, pulmonary embolism, venous thromboembolism, biomarkersAbstract
Pulmonary embolism (PE), a major manifestation of venous thromboembolism (VTE), is a potentially fatal condition involving complex inflammatory and procoagulant mechanisms. P-selectin, a cell adhesion molecule expressed on activated endothelial cells and platelets, plays a central role in thrombogenesis by mediating leukocyte-platelet- endothelium interactions and triggering the coagulation cascade. Elevated plasma P-selectin levels have been associated with increased risk of deep vein thrombosis and pulmonary embolism, supporting its role as a diagnostic and prognostic biomarker. Furthermore, P-selectin is implicated in various other disorders, including cancer, chronic inflammatory diseases, and inherited thrombophilias. Targeted anti-P-selectin therapies, including monoclonal antibodies and novel inhibitors, represent a promising direction in the prevention and management of thrombotic events. This article provides a detailed analysis of the pathophysiological role, predictive value, and therapeutic potential of P-selectin in the context of PE and thrombotic disorders.
References
=Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41:543–603. doi:10.1093/eurheartj/ehz405.
Tarbox AK, Swaroop M. Pulmonary embolism. Int J Crit Illn Inj Sci. 2013;3(1):69–72.
Horlander KT, Mannino DM, Leeper KV. Pulmonary embolism mortality in the United States. Arch Intern Med. 2003;163(14):1711–1717.
Wendelboe AM. Global health burden of venous thromboembolism. Arterioscler Thromb Vasc Biol. 2024;44:1007–1011.
Kumar DR, Hanlin A, Glurich I, Mazza JJ, Yale SH. Virchow’s contribution to the understanding of thrombosis and cellular biology. Clin Med Res. 2010;8(3–4):168–172.
Shah IK, Patel B, Desai M, Johnson C, Vora R, Lee J, et al. Pathophysiology and management of pulmonary embolism. Int J Angiol. 2022;31(3):143–149.
Turetz M, Sideris AT, Friedman OA, Triphathi N, Horowitz JM. Epidemiology, pathophysiology, and natural history of pulmonary embolism. Semin Intervent Radiol. 2018;35(2):92–98.
Escopy S, Chaikof EL. Targeting the P-selectin/ PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation. Blood Vessels Thromb Haemost. 2024;1(3):100015.
Ludwig RJ, Berghoff AS, Gerdes S, Scholz J, Tandler N, Utikal J, et al. P-selectin – a common therapeutic target for cardiovascular disorders, inflammation, and tumour metastasis. Expert Opin Ther Targets. 2007;11(8):1043–1053.
McEver RP. Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res. 2015;107(3):331–339.
Lorant DE, Topham MK, Whatley RE, McEver RP, McIntyre TM, Prescott SM, et al. Inflammatory roles of P-selectin. J Clin Invest. 1993;92(2):559–570.
Ramos CL, Huo Y, Jung U, Ghosh S, Manka DR, Sarembock IJ, et al. Direct demonstration of P-selectin- and VCAM-1-dependent mononuclear cell rolling in early atherosclerotic lesions of apolipoprotein E-deficient mice. Circ Res. 1999;84(11):1237–1244. doi:10.1161/01.res.84.11.1237.
Nabi F, Spiro TP, Johnson CJ, Van Wagoner DR, Ahmad M. Effect of P-selectin on phosphatidylserine exposure and surface-dependent thrombin generation on monocytes. Arterioscler Thromb Vasc Biol. 2005;25(5):1065–1070.
Kutlar A, Kutlar F, Embury SH. Cellular adhesion and the endothelium. Hematol Oncol Clin North Am. 2014;28(2):323–339. doi:10.1016/j.hoc.2013.11.008.
Mezouar S, Frère C, Darbousset R, Mege D, Crescence L, Dignat-George F, et al. Role of P-Selectin in Cancer- Associated Thrombosis and Tumor Progression. Int J Mol Sci. 2021;22(15):7942.
Karki NR. P-Selectin Blockade in the Treatment of Painful Vaso-Occlusive Crises in Sickle Cell Disease: A Spotlight on Crizanlizumab. J Pain Res. 2021;14:849–856.
Purdy M, Al-Tamimi M, Lip GYH, Watson SP, Pasi KJ. P- and E-selectin in venous thrombosis and non-venous pathologies. J Thromb Haemost. 2022;20:1056–1066.
Swamy S, Sundararajan V, Karunakaran D, Jayaraman B. Plasma levels of P-selectin and future risk of incident venous thromboembolism. J Thromb Haemost. 2023;21(9):2451–2460.
Mario-Oblitas C, Ramos Y, Marín-Restrepo LM, Espinoza J, Alfaro RA, Sanchez JL, et al. Evaluation of soluble P-selectin as a predictive biomarker in acute symptomatic pulmonary embolism. Eur J Haematol. 2024;113(2):141–148.
Erpenbeck L, Schön MP. Deadly allies: The fatal interplay between platelets and metastasizing cancer cells. Blood. 2010;115:3427–3436.
Yeini E, Satchi-Fainaro R. The role of P-selectin in cancer-associated thrombosis and beyond. Thromb Res. 2022;213(Suppl 1):S22–S28.
Fernandes LFB, Tricarico PM, Cesselli D, Castiglia G, Bulfoni M, Tell G, et al. Role of P-selectin in thromboembolic events in patients with cancer. Mol Clin Oncol. 2017;8(1):188–196.
de Williage SU, Schmidt R, Grammer TB, Kleber ME, Delgado G, März W. Selectin haplotypes and the risk of venous thrombosis: influence of linkage disequilibrium with the factor V Leiden mutation. J Thromb Haemost. 2008;6:478–485.
Diz-Kucukkaya R, Hancer VS, Sari I, Buyukasik Y, Haznedaroglu IC, Goker H. P-selectin glycoprotein ligand-1 VNTR polymorphisms and risk of thrombosis in the antiphospholipid syndrome. Ann Rheum Dis. 2007;66(10):1378–1380.
Mehta A, Lee SJ, Finkelstein D, Greenberg JA, Halene S, Kentsis A, et al. Plasma P-selectin is an early marker of thromboembolism in COVID-19. J Emerg Med. 2021. doi:10.1101/2021.07.10.21260293.
Voskaridou E, Christoulas D, Zervas K, Katodritou E, Terpos E. Soluble P-Selectin Levels in Patients with Sickle Cell Disease Reflect Platelets’ Activation Rather Than Endothelial Dysfunction. Blood. 2019;134(Suppl 1):4829.
Schneider DJ, Sobel BE, Dai X, McMahon TJ, Lefer AM. Association between increased platelet P-selectin expression and obesity in patients with type 2 diabetes. Diabetes Care. 2009;32(5):944–949.
Gerlach H. The influence of sex hormones on thrombosis and platelet activation: implications for female cardiovascular health. Thromb Res. 2016;139:19–25.
Ramacciotti E, Hawley AE, Farris DM, Ballard NE, Wrobleski SK, Myers DD, et al. P-selectin/PSGL- 1 inhibitors versus enoxaparin in the resolution of venous thrombosis: A meta-analysis. Thromb Res. 2010;125(4):e138–e142.
Escopy S, Chaikof EL. Targeting the P-selectin/ PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation. Blood Vessels Thromb Haemost. 2024;1(3):100015
Downloads
Published
License
Copyright (c) 2025 Bulletin of the Academy of Sciences of Moldova. Medical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
