Skip to main content

Advertisement

Log in

Patients with autoimmune chronic inflammatory diseases present increased biomarkers of thromboinflammation and endothelial dysfunction in the absence of flares and cardiovascular comorbidities

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Cardiovascular risk is increased in patients with autoimmune rheumatic diseases. Endothelial, erythrocyte and platelet microvesicles (MVs) are elevated in patients with cardiovascular diseases and represent novel markers of endothelial dysfunction and thromboinflammation. We tested whether their levels are increased in patients with autoimmune rheumatic diseases (ARDs) in the absence of disease flare and cardiovascular comorbidities. Well-controlled patients with rheumatoid arthritis or systemic lupus erythematosus were studied, provided they were free from cardiovascular comorbidities and established cardiovascular disease. We additionally studied (a) a control group consisting of healthy volunteers and (b) a reference group including patients with stable coronary artery disease (CAD). MVs were measured using a standardized flow cytometry protocol. In a population of 74 participants, patients with ARDs (n = 17) presented increased levels of both endothelial (283.3 ± 195.0/μL vs 168.5 ± 54.8/μL, p = 0.029) and platelet MVs (374.0 ± 275.3/μL vs 225.7 ± 101.1/μL, p = 0.046) compared to controls (n = 34), whereas erythrocyte MVs did not significantly differ. In addition, patients with ARDs showed similar levels of endothelial MVs compared to CAD patients (n = 23) (283.3 ± 195.0/μL vs 297.0 ± 211.8/μL, p = 0.846). Platelet MVs were significantly associated with disease duration, and erythrocyte MVs with patients’ perceived disease activity. In conclusion, increased levels of endothelial and platelet MVs may be evident in patients with ARDs, even in the absence of disease flares and before the establishment of cardiovascular complications. Levels of endothelial MVs resemble those of patients with profound atherothrombotic profile. The prognostic potential of MVs in terms of cardiovascular disease prevention warrants further investigation in patients with ARDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

References

  1. Anyfanti P, Gavriilaki E, Douma S, Gkaliagkousi E (2020) Endothelial dysfunction in patients with rheumatoid arthritis: the role of hypertension. Curr Hypertens Rep 22:56

    Article  CAS  Google Scholar 

  2. Anyfanti P, Triantafyllou A, Gkaliagkousi E et al (2017) Subendocardial viability ratio in patients with rheumatoid arthritis: comparison with healthy controls and identification of prognostic factors. Clin Rheumatol 36:1229–1236. https://doi.org/10.1007/s10067-017-3659-9

    Article  PubMed  Google Scholar 

  3. Anyfanti P, Triantafyllou A, Gkaliagkousi E et al (2017) Retinal vessel morphology in rheumatoid arthritis: association with systemic inflammation, subclinical atherosclerosis and cardiovascular risk. Microcirculation. https://doi.org/10.1111/micc.12417

    Article  PubMed  Google Scholar 

  4. Anyfanti P, Gkaliagkousi E, Triantafyllou A et al (2018) Dermal capillary rarefaction as a marker of microvascular damage in patients with rheumatoid arthritis: association with inflammation and disorders of the macrocirculation. Microcirculation 25:e12451. https://doi.org/10.1111/micc.12451

    Article  CAS  PubMed  Google Scholar 

  5. Koletsos N, Gkaliagkousi E, Lazaridis A et al (2021) Skin microvascular dysfunction in patients with systemic lupus erythematosus with and without cardiovascular risk factors. Rheumatology 60:2834–2841. https://doi.org/10.1093/rheumatology/keaa722

  6. Gkaliagkousi E, Gavriilaki E, Triantafyllou A, Douma S (2015) Clinical significance of endothelial dysfunction in essential hypertension. Curr Hypertens Rep. https://doi.org/10.1007/s11906-015-0596-3

    Article  PubMed  Google Scholar 

  7. Van Es N, Bleker S, Sturk A, Nieuwland R (2015) Clinical significance of tissue factor-exposing microparticles in arterial and venous thrombosis. Semin Thromb Hemost 41:718–727. https://doi.org/10.1055/s-0035-1556047

    Article  CAS  PubMed  Google Scholar 

  8. Lipets EN, Antonova OA, Shustova ON et al (2020) Use of Thrombodynamics for revealing the participation of platelet, erythrocyte, endothelial, and monocyte microparticles in coagulation activation and propagation. PLoS One 15:e0227932. https://doi.org/10.1371/journal.pone.0227932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gkaliagkousi E, Gavriilaki E, Vasileiadis I et al (2019) Endothelial microvesicles circulating in peripheral and coronary circulation are associated with central blood pressure in coronary artery disease. Am J Hypertens 32:1199–1205. https://doi.org/10.1093/ajh/hpz116

    Article  CAS  PubMed  Google Scholar 

  10. Gkaliagkousi E, Nikolaidou B, Gavriilaki E et al (2019) Increased erythrocyte- and platelet-derived microvesicles in newly diagnosed type 2 diabetes mellitus. Diabetes Vasc Dis Res 16:458–465. https://doi.org/10.1177/1479164119844691

    Article  CAS  Google Scholar 

  11. Gkaliagkousi E, Gavriilaki E, Yiannaki E et al (2021) Platelet microvesicles are associated with the severity of coronary artery disease: comparison between peripheral and coronary circulation. J Thromb Thrombolysis. https://doi.org/10.1007/s11239-020-02302-5

    Article  PubMed  Google Scholar 

  12. Ridger VC, Boulanger CM, Angelillo-Scherrer A et al (2017) Microvesicles in vascular homeostasis and diseases. Thromb Haemost 117:1296–1316. https://doi.org/10.1160/th16-12-0943

    Article  PubMed  Google Scholar 

  13. Bruce B, Fries JF (2005) The health assessment questionnaire (HAQ). Clin Exp Rheumatol 23(5 Suppl 39):S14-8

  14. World Medical Association (2013) World medical association declaration of helsinki: ethical principles for medical research involving human subjects. JAMA 310:2191–2194. https://doi.org/10.1001/jama.2013.281053

  15. Bordy R, Totoson P, Prati C et al (2018) Microvascular endothelial dysfunction in rheumatoid arthritis. Nat Rev Rheumatol 14:404–420. https://doi.org/10.1038/s41584-018-0022-8

    Article  CAS  PubMed  Google Scholar 

  16. Frangou E, Chrysanthopoulou A, Mitsios A et al (2019) REDD1_autophagy pathway promotes thromboinflammation and fibrosis in human systemic lupus erythematosus (SLE). Ann Rheum Dis 78:238–248

    Article  CAS  Google Scholar 

  17. Kambas K, Chrysanthopoulou A, Vassilopoulos D et al (2013) Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease. Ann Rheum Dis 73:1854–1863

    Article  Google Scholar 

  18. Rodríguez-Carrio J, Alperi-López M, López P et al (2015) Altered profile of circulating microparticles in rheumatoid arthritis patients. Clin Sci 128:437–448. https://doi.org/10.1042/CS20140675

    Article  CAS  Google Scholar 

  19. Pamuk GE, Vural Ö, Turgut B et al (2008) Increased platelet activation markers in rheumatoid arthritis: are they related with subclinical atherosclerosis? Platelets 19:146–154. https://doi.org/10.1080/09537100701210057

    Article  CAS  PubMed  Google Scholar 

  20. Gitz E, Pollitt AY, Gitz-francois JJ et al (2016) CLEC-2 expression is maintained on activated platelets and on platelet microparticles. Blood 124:2262–2271. https://doi.org/10.1182/blood-2014-05-572818.The

    Article  Google Scholar 

  21. Knijff-Dutmer EAJ, Koerts J, Nieuwland R et al (2002) Elevated levels of platelet microparticles are associated with disease activity in rheumatoid arthritis. Arthritis Rheum 46:1498–1503. https://doi.org/10.1002/art.10312

    Article  CAS  PubMed  Google Scholar 

  22. Pereira J, Alfaro G, Goycoolea M et al (2006) Circulating platelet-derived microparticles in systemic lupus erythematosus. Thromb Haemost 95:94–99. https://doi.org/10.1160/th05-05-0310

    Article  CAS  PubMed  Google Scholar 

  23. Sellam J, Proulle V, Jüngel A et al (2009) Increased levels of circulating microparticles in primary Sjögren’s syndrome, systemic lupus erythematosus and rheumatoid arthritis and relation with disease activity. Arthritis Res Ther 11:1–11. https://doi.org/10.1186/ar2833

    Article  CAS  Google Scholar 

  24. Nielsen CT, Østergaard O, Johnsen C et al (2011) Distinct features of circulating microparticles and their relationship to clinical manifestations in systemic lupus erythematosus. Arthritis Rheum 63:3067–3077. https://doi.org/10.1002/art.30499

    Article  PubMed  Google Scholar 

  25. Erdbruegger U, Grossheim M, Hertel B et al (2008) Diagnostic role of endothelial microparticles in vasculitis. Rheumatology 47:1820–1825. https://doi.org/10.1093/rheumatology/ken373

    Article  CAS  PubMed  Google Scholar 

  26. Brogan PA, Shah V, Brachet C et al (2004) Endothelial and platelet microparticles in vasculitis of the young. Arthritis Rheum 50:927–936. https://doi.org/10.1002/art.20199

    Article  CAS  PubMed  Google Scholar 

  27. Bartoloni E, Alunno A, Bistoni O et al (2015) Characterization of circulating endothelial microparticles and endothelial progenitor cells in primary Sjögren’s syndrome: new markers of chronic endothelial damage? Rheumatol (United Kingdom) 54:536–544. https://doi.org/10.1093/rheumatology/keu320

    Article  CAS  Google Scholar 

  28. López P, Rodríguez-Carrio J, Martínez-Zapico A et al (2017) Circulating microparticle subpopulations in systemic lupus erythematosus are affected by disease activity. Int J Cardiol 236:138–144. https://doi.org/10.1016/j.ijcard.2017.02.107

    Article  PubMed  Google Scholar 

Download references

Funding

This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning 2014–2020” in the context of the project “Evaluation of novel markers of endothelial dysfunction and thrombotic microenvironment in patients with rheumatoid arthritis: association with markers of subclinical inflammation and cardiovascular damage (MIS 5047870)”. Authors funded: PA, EGa, MD, EGk.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Panagiota Anyfanti.

Ethics declarations

Conflict of interest

The author declares that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Anyfanti, P., Gavriilaki, E., Nikolaidou, B. et al. Patients with autoimmune chronic inflammatory diseases present increased biomarkers of thromboinflammation and endothelial dysfunction in the absence of flares and cardiovascular comorbidities. J Thromb Thrombolysis 53, 10–16 (2022). https://doi.org/10.1007/s11239-021-02517-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-021-02517-0

Keywords

Navigation