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A study of endothelial and platelet microvesicles across different hypertension phenotypes

Journal of Human Hypertension volume 36, pages 561–569 (2022)Cite this article

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Abstract

Rather than being mere biomarkers reflecting generalized vascular injury, endothelial- (EMVs) and platelet-derived (PMVs) microvesicles have emerged as potent regulators of intercellular communication with significant biologic effects in vascular homeostasis and several pathophysiological responses including inflammation and thrombosis. So far, studies in hypertension are scarce, whereas no studies exist in masked hypertension (MH). We measured EMVs and PMVs in untreated, newly diagnosed hypertensives (HTs) and MHs compared to normotensive controls (NTs), and associated them with various cardiovascular risk factors. Sustained hypertension (SHT) and MH were defined according to standard blood pressure (BP) criteria. All HTs were free of cardiovascular disease and medications. Microvesicles’ quantitation and detection were performed by flow cytometry by using cell-specific antibodies and corresponding isotypes (anti-CD105 and anti-CD144 for EMVs, anti-CD42a for PMVs, and Annexin V–fluorescein isothiocyanate for all microvesicles). In this study, we included 59 HTs (44 SHTs and 15 MHs) and 27 NTs. HTs had significantly elevated EMVs (p = 0.004), but not PMVs compared to NTs. MHs had significantly elevated EMVs compared to NTs (p = 0.012) but not compared to SHTs. Furthermore, EMVs significantly correlated with ambulatory (r = 0.214–0.284), central BP (r = 0.247–0.262), and total vascular resistance (r = 0.327–0.361). EMVs are increased not only in SHTs but also in MHs, a hypertension phenotype with a cardiovascular risk close to SHT. EMVs have emerged as active contributors to thromboinflammation and vascular damage and may explain, in part, the adverse cardiovascular profile of SHTs and MHs.

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Fig. 1: Comparison of plasma levels of endothelial microvesicles (EMVs) in different phenotypes of hypertension and normotensive individuals.
Fig. 2: Correlation plots depicting the association between endothelial microvesicles (EMVs) and various blood pressure (BP) parameters in the total study population.

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References

  1. Arraud N, Linares R, Tan S, Gounou C, Pasquet JM, Mornet S, et al. Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration. J Thromb Haemost. 2014;12:614–27.

    Article  CAS  Google Scholar 

  2. Ridger V, Boulanger C, Angelillo-Scherrer A, Badimon L, Blanc-Brude O, Bochaton-Piallat M, et al. Microvesicles in vascular homeostasis and diseases. Position Paper of the European Society of Cardiology (ESC) Working Group on Atherosclerosis and Vascular Biology. Thromb Haemost. 2017;117:1296–316.

    Article  Google Scholar 

  3. Mause SF, Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res. 2010;107:1047–57.

    Article  CAS  Google Scholar 

  4. Burger D, Schock S, Thompson CS, Montezano AC, Hakim AM, Touyz RM. Microparticles: biomarkers and beyond. Clin Sci. 2013;124:423–41.

    Article  CAS  Google Scholar 

  5. Dignat-George F, Boulanger CM. The many faces of endothelial microparticles. Arterioscler Thromb Vasc Biol. 2011;31:27–33.

    Article  CAS  Google Scholar 

  6. Leroyer AS, Anfosso F, Lacroix R, Sabatier F, Simoncini S, Njock SM, et al. Endothelial-derived microparticles: biological conveyors at the crossroad of inflammation, thrombosis and angiogenesis. Thromb Haemost. 2010;104:456–63.

    Article  CAS  Google Scholar 

  7. Sinning JM, Losch J, Walenta K, Böhm M, Nickenig G, Werner N. Circulating CD31 +/Annexin V + microparticles correlate with cardiovascular outcomes. Eur Heart J. 2011;32:2034–41.

    Article  CAS  Google Scholar 

  8. Yong PJA, Koh CH, Shim WSN. Endothelial microparticles: missing link in endothelial dysfunction? Eur J Prev Cardiol. 2013;20:496–512.

    Article  Google Scholar 

  9. Aatonen M, Grönholm M, Siljander PM. Platelet-derived microvesicles: multitalented participants in intercellular communication. Semin Thromb Hemost. 2012;38:102–13.

    Article  CAS  Google Scholar 

  10. Melki I, Tessandier N, Zufferey A, Boilard E. Platelet microvesicles in health and disease. Platelets. 2017;28:214–21.

    Article  CAS  Google Scholar 

  11. Amabile N, Rautou PE, Tedgui A, Boulanger CM. Microparticles: key protagonists in cardiovascular disorders. Semin Thromb Hemost. 2010;1:907–16.

    Article  Google Scholar 

  12. Voukalis C, Shantsila E, Lip GYH. Microparticles and cardiovascular diseases. Ann Med. 2019;51:193–223.

    Article  Google Scholar 

  13. Gkaliagkousi E, Gavriilaki E, Yiannaki E, Vasileiadis I, Nikolaidou B, Lazaridis A, et al. Platelet microvesicles are associated with the severity of coronary artery disease: comparison between peripheral and coronary circulation. J Thromb Thrombolysis. 2020.

  14. Gkaliagkousi E, Nikolaidou B, Gavriilaki E, Lazaridis A, Yiannaki E, Anyfanti P, et al. Increased erythrocyte- and platelet-derived microvesicles in newly diagnosed type 2 diabetes mellitus. Diabetes Vasc Dis Res. 2019;16:458–65.

  15. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. ESC/ESH Guidelines for the management of arterial hypertension. J Hypertens. 2018;36:1953–2041.

    Article  CAS  Google Scholar 

  16. Gkaliagkousi E, Corrigall V, Becker S, De WP, Shah A, Zamboulis C, et al. Decreased platelet nitric oxide contributes to increased circulating monocyte-platelet aggregates in hypertension. Eur Hear J. 2009;30:3048–54.

    Article  CAS  Google Scholar 

  17. Gkaliagkousi E, Gavriilaki E, Triantafyllou A, Douma S. Clinical significance of endothelial dysfunction in essential hypertension. Curr Hypertens Rep. 2015;17:85.

    Article  Google Scholar 

  18. Preston RA, Jy W, Jimenez JJ, Mauro LM, Horstman LL, Valle M, et al. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension. 2003;41:211–7.

    Article  CAS  Google Scholar 

  19. Stockelman KA, Hijmans JG, Bammert T, Greiner J, Stauffer BL, DeSouza CA. Circulating endothelial cell derived microvesicles are elevated with hypertension and associated with endothelial dysfunction. Can J Physiol Pharmacol. 2020;98:557–61.

    Article  CAS  Google Scholar 

  20. Sansone R, Baaken M, Horn P, Schuler D, Westenfeld R, Amabile N, et al. Release of endothelial microparticles in patients with arterial hypertension, hypertensive emergencies and catheter-related injury. Atherosclerosis. 2018;273:67–74.

    Article  CAS  Google Scholar 

  21. Hu S, Zhang H, Zhang Q, Xiu R. CD144 + EMPs / CD62E + EMPs: a couple of new biomarkers to monitor endothelial function in hypertension with hyperlipidemia involved. Int J Cardiol. 2014;175:203.

    Article  Google Scholar 

  22. Robert S, Poncelet P, Lacroix R. Standardization of platelet-derived microparticle counting using calibrated beads and a Cytomics FC500 routine flow cytometer: a first step towards multicenter studies? J Thromb Haemost. 2009;7:190–7.

    Article  CAS  Google Scholar 

  23. Witwer KW, Buzás EI, Bemis LT, Bora A, Lässer C, Lötvall J, et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles. 2013;2:20360.

  24. Berezin A, Zulli A, Kerrigan S, Petrovic D, Kruzliak P. Predictive role of circulating endothelial-derived microparticles in cardiovascular diseases. Clin Biochem. 2015;48:562–8.

    Article  CAS  Google Scholar 

  25. Tomaniak M, Gąsecka A, Filipiak KJ. Cell-derived microvesicles in cardiovascular diseases and antiplatelet therapy monitoring—a lesson for future trials? Current evidence, recent progresses and perspectives of clinical application. Int J Cardiol. 2017;226:93–102.

    Article  Google Scholar 

  26. Bernal-Mizrachi L, Jy W, Jimenez JJ, Pastor J, Mauro LM, Horstman LL, et al. High levels of circulating endothelial microparticles in patients with acute coronary syndromes. Am Heart J. 2003;145:962–70.

    Article  Google Scholar 

  27. El-Gamal H, Parray AS, Mir FA, Shuaib A, Agouni A. Circulating microparticles as biomarkers of stroke: a focus on the value of endothelial- and platelet-derived microparticles. J Cell Physiol. 2019;234:16739–54.

    Article  CAS  Google Scholar 

  28. Li S, Wei J, Zhang C, Li X, Meng W, Mo X, et al. Cell-derived microparticles in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Cell Physiol Biochem. 2016;39:2439–50.

    Article  CAS  Google Scholar 

  29. Suades R, Padró T, Alonso R, Mata P, Badimon L. Lipid-lowering therapy with statins reduces microparticle shedding from endothelium, platelets and inflammatory cells. Thromb Haemost. 2013;110:366–77.

    Article  CAS  Google Scholar 

  30. Bulut D, Becker V, Mügge A. Acetylsalicylate reduces endothelial and platelet-derived microparticles in patients with coronary artery disease. Can J Physiol Pharmacol. 2011;89:239–44.

    Article  CAS  Google Scholar 

  31. Danielle Tientcheu C, Ayers SR, Das DK, McGuire JA, de L, Amit K, et al. Target organ complications and cardiovascular events associated with masked hypertension and white-coat hypertension: analysis from the Dallas Heart Study. J Am Coll Cardiol. 2016;66:2159–69.

    Article  Google Scholar 

  32. Gkaliagkousi E, Gavriilaki E, Triantafyllou A, Nikolaidou B, Anyfanti P, Koletsos N, et al. Asymmetric dimethylarginine levels are associated with augmentation index across naïve untreated patients with different hypertension phenotypes. J Clin Hypertens. 2018;20:680–5.

    Article  CAS  Google Scholar 

  33. Caliskan M, Ciftci O, Gullu H, Caliskan Z, Güven A, Erdogan D, et al. Effect of masked, white-coat, and sustained hypertension on coronary flow reserve and peripheral endothelial functions. Clin Exp Hypertens. 2013;35:183–91.

    Article  Google Scholar 

  34. Wang J, Zhong Y, Ma X, Xiao X, Cheng C, Chen Y, et al. Analyses of endothelial cells and endothelial progenitor cells released microvesicles by using microbead and Q-dot based nanoparticle tracking analysis. Sci Rep. 2016;6:1–10.

    Google Scholar 

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Authors and Affiliations

  1. 3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Antonios Lazaridis, Eleni Gavriilaki, Barbara Nikolaidou, Panagiotis Dolgyras, Panagiota Anyfanti, Areti Triantafyllou, Nikolaos Koletsos, Stella Douma & Eugenia Gkaliagkousi

  2. Department of Hematology, Theagenion Cancer Center, Thessaloniki, Greece

    Efi Yiannaki & Dimitra Markala

  3. Northern Greece Statistics Directorate, Hellenic Statistical Authority, Thessaloniki, Greece

    Christos Tzimos

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  1. Antonios Lazaridis
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  2. Eleni Gavriilaki
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Correspondence to Eugenia Gkaliagkousi.

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Lazaridis, A., Gavriilaki, E., Nikolaidou, B. et al. A study of endothelial and platelet microvesicles across different hypertension phenotypes. J Hum Hypertens 36, 561–569 (2022). https://doi.org/10.1038/s41371-021-00531-6

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