P- and E- Selectin in Venous Thrombosis and Non-venous Pathologies

Overview

Journal J Thromb Haemost

Publisher Elsevier

Specialty Hematology

Date 2022 Mar 4

PMID 35243742

Authors

Megan Purdy

Andrea Obi

Daniel Myers

Thomas Wakefield

Affiliations

Soon will be listed here.

Abstract

Venous thromboembolism is a very common and costly health problem worldwide. Anticoagulant treatment for VTE is imperfect: all have the potential for significant bleeding, and none prevent the development of post thrombotic syndrome after deep vein thrombosis or chronic thromboembolic pulmonary hypertension after pulmonary embolism. For these reasons, alternate forms of therapy with improved efficacy and decreased bleeding are needed. Selectins are a family (P-selectin, E-selectin, L-selectin) of glycoproteins that facilitate and augment thrombosis, modulating neutrophil, monocyte, and platelet activity. P- and E-selectin have been investigated as potential biomarkers for thrombosis. Inhibition of P-selectin and E-selectin decrease thrombosis and vein wall fibrosis, with no increase in bleeding. Selectin inhibition is a promising avenue of future study as either a stand-alone treatment for VTE or as an adjunct to standard anticoagulation therapies.

Citing Articles

Homologous-adhering/targeting cell membrane- and cell-mediated delivery systems: a cancer-catch-cancer strategy in cancer therapy.

Liu C, Gao J, Cheng Y, Zhang S, Fu C Regen Biomater. 2025; 12:rbae135.

PMID: 39811105 PMC: 11729729. DOI: 10.1093/rb/rbae135.

Thrombotic Risk Assessment, P-Selectin, and Thromboprophylaxis Use Among, Cancer Patients at the University of Calabar Teaching Hospital, Calabar.

Akaba K, Akaba E, Oshatuyi O, Ssenkumba B J Blood Med. 2024; 15:501-512.

PMID: 39697764 PMC: 11654208. DOI: 10.2147/JBM.S478192.

First-in-human study of Tc-labeled fucoidan, a SPECT tracer targeting P-selectin.

Oostveen R, Zheng K, Kaiser Y, Nurmohamed N, Kroon J, de Wit T EJNMMI Res. 2024; 14(1):112.

PMID: 39562382 PMC: 11576749. DOI: 10.1186/s13550-024-01173-8.

The Molecular Mechanisms of Portal Vein Thrombosis in Hepatocellular Carcinoma.

Galasso L, Cerrito L, Termite F, Mignini I, Esposto G, Borriello R Cancers (Basel). 2024; 16(19).

PMID: 39409869 PMC: 11482560. DOI: 10.3390/cancers16193247.

Cutting edge of immune response and immunosuppressants in allogeneic and xenogeneic islet transplantation.

Yue L, Li J, Yao M, Song S, Zhang X, Wang Y Front Immunol. 2024; 15:1455691.

PMID: 39346923 PMC: 11427288. DOI: 10.3389/fimmu.2024.1455691.

References

Japp A, Chelliah R, Tattersall L, Lang N, Meng X, Weisel K . Effect of PSI-697, a novel P-selectin inhibitor, on platelet-monocyte aggregate formation in humans. J Am Heart Assoc. 2013; 2(1):e006007. PMC: 3603266. DOI: 10.1161/JAHA.112.006007. View

Baldwin M, Moore H, Rudarakanchana N, Gohel M, Davies A . Post-thrombotic syndrome: a clinical review. J Thromb Haemost. 2013; 11(5):795-805. DOI: 10.1111/jth.12180. View

Purdy M, Obi A, Myers D, Wakefield T . P- and E- selectin in venous thrombosis and non-venous pathologies. J Thromb Haemost. 2022; 20(5):1056-1066. PMC: 9314977. DOI: 10.1111/jth.15689. View

Dzikowska-Diduch O, Domienik-Karlowicz J, Gorska E, Demkow U, Pruszczyk P, Kostrubiec M . E-selectin and sICAM-1, biomarkers of endothelial function, predict recurrence of venous thromboembolism. Thromb Res. 2017; 157:173-180. DOI: 10.1016/j.thromres.2017.07.027. View

Comer S, Cullivan S, Szklanna P, Weiss L, Cullen S, Kelliher S . COVID-19 induces a hyperactive phenotype in circulating platelets. PLoS Biol. 2021; 19(2):e3001109. PMC: 7920383. DOI: 10.1371/journal.pbio.3001109. View

Myers D, Hawley A, Farris D, Wrobleski S, Thanaporn P, Schaub R . P-selectin and leukocyte microparticles are associated with venous thrombogenesis. J Vasc Surg. 2003; 38(5):1075-89. DOI: 10.1016/s0741-5214(03)01033-4. View

Jamaly S, Basavaraj M, Starikova I, Olsen R, Braekkan S, Hansen J . Elevated plasma levels of P-selectin glycoprotein ligand-1-positive microvesicles in patients with unprovoked venous thromboembolism. J Thromb Haemost. 2018; . DOI: 10.1111/jth.14162. View

Obi A, Andraska E, Kanthi Y, Kessinger C, Elfline M, Luke C . Endotoxaemia-augmented murine venous thrombosis is dependent on TLR-4 and ICAM-1, and potentiated by neutropenia. Thromb Haemost. 2016; 117(2):339-348. PMC: 5436925. DOI: 10.1160/TH16-03-0218. View

Jilma B, Marsik C, Kovar F, Wagner O, Jilma-Stohlawetz P, Endler G . The single nucleotide polymorphism Ser128Arg in the E-selectin gene is associated with enhanced coagulation during human endotoxemia. Blood. 2004; 105(6):2380-3. DOI: 10.1182/blood-2004-09-3752. View

10.

Girao-Silva T, Fonseca-Alaniz M, Ribeiro-Silva J, Lee J, Patil N, Dallan L . High stretch induces endothelial dysfunction accompanied by oxidative stress and actin remodeling in human saphenous vein endothelial cells. Sci Rep. 2021; 11(1):13493. PMC: 8242094. DOI: 10.1038/s41598-021-93081-3. View

11.

Gremmel T, Ay C, Seidinger D, Pabinger I, Panzer S, Koppensteiner R . Soluble p-selectin, D-dimer, and high-sensitivity C-reactive protein after acute deep vein thrombosis of the lower limb. J Vasc Surg. 2011; 54(6 Suppl):48S-55S. DOI: 10.1016/j.jvs.2011.05.097. View

12.

Culmer D, Dunbar M, Hawley A, Sood S, Sigler R, Henke P . E-selectin inhibition with GMI-1271 decreases venous thrombosis without profoundly affecting tail vein bleeding in a mouse model. Thromb Haemost. 2017; 117(6):1171-1181. DOI: 10.1160/TH16-04-0323. View

13.

Stahli B, Gebhard C, Duchatelle V, Cournoyer D, Petroni T, Tanguay J . Effects of the P-Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention According to Timing of Infusion: Insights From the SELECT-ACS Trial. J Am Heart Assoc. 2016; 5(11). PMC: 5210344. DOI: 10.1161/JAHA.116.004255. View

14.

McEver R . Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res. 2015; 107(3):331-9. PMC: 4592324. DOI: 10.1093/cvr/cvv154. View

15.

Bittar L, da Silva L, Orsi F, Zapponi K, Mazetto B, De Paula E . Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome. PLoS One. 2020; 15(1):e0227150. PMC: 6964981. DOI: 10.1371/journal.pone.0227150. View

16.

Anderson I, Cifu A . Management of Bleeding in Patients Taking Oral Anticoagulants. JAMA. 2018; 319(19):2032-2033. DOI: 10.1001/jama.2018.3504. View

17.

Delis K, Bountouroglou D, Mansfield A . Venous claudication in iliofemoral thrombosis: long-term effects on venous hemodynamics, clinical status, and quality of life. Ann Surg. 2003; 239(1):118-26. PMC: 1356201. DOI: 10.1097/01.sla.0000103067.10695.74. View

18.

Morikis V, Chase S, Wun T, Chaikof E, Magnani J, Simon S . Selectin catch-bonds mechanotransduce integrin activation and neutrophil arrest on inflamed endothelium under shear flow. Blood. 2017; 130(19):2101-2110. PMC: 5680610. DOI: 10.1182/blood-2017-05-783027. View

19.

Wun T, Styles L, DeCastro L, Telen M, Kuypers F, Cheung A . Phase 1 study of the E-selectin inhibitor GMI 1070 in patients with sickle cell anemia. PLoS One. 2014; 9(7):e101301. PMC: 4079300. DOI: 10.1371/journal.pone.0101301. View

20.

Matusov Y, Singh I, Yu Y, Chun H, Maron B, Tapson V . Chronic Thromboembolic Pulmonary Hypertension: the Bedside. Curr Cardiol Rep. 2021; 23(10):147. PMC: 8375459. DOI: 10.1007/s11886-021-01573-5. View