Skip to main content

Advertisement

SpringerLink
Log in

Procoagulant effect of extracellular vesicles in patients after transcatheter aortic valve replacement or transcatheter aortic valve replacement with percutaneous coronary intervention

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

Abstract

Patients with severe aortic stenosis (AS) after replacement of the transcatheter aortic valve (TAVR) are more likely to develop thrombotic complications such as cerebral embolism and artificial valve thrombosis. However, the mechanism is not yet well defined. We aimed to explore the plasma extracellular vesicles (EVs) levels and their role in the induction of procoagulant activity (PCA) in patients receiving TAVR alone or TAVR with percutaneous coronary intervention (PCI). EVs were analyzed with flow cytometer. Markers of platelet and endothelial cell activation were quantified using selective enzyme-linked immunosorbent assay (ELISA) kits. Procoagulant activity (PCA) was assessed by clotting time, purified clotting complex assays, and fibrin production assays. Our results confirmed that EVs with positive phosphatedylserin (PS+EV), platelet EVs (PEVs) and positive tissue factor EVs (TF+EVs) were higher in patients following TAVR than before TAVR, particularly in TAVR with PCI. Furthermore, endothelial-derived EVs (EEVs) were also higher in patients after TAVR with PCI than pre-TAVR, however, the EEVs levels in TAVR alone patients were gradually reduce than pre-TAVR. In addition, we further proved that total EVs contributed to dramatically shortened coagulation time, increased intrinsic/extrinsic factor Xa and thrombin generation in patients after TAVR, especially in TAVR with PCI. The PCA was markedly attenuated by approximately 80% with lactucin. Our study reveals a previously unrecognized link between plasma EV levels and hypercoagulability in patients after TAVR, especially TAVR with PCI. Blockade of PS+EVs may improve the hypercoagulable state and prognosis of patients.

Highlights

  • Patients after TAVR, especially TAVR with PCI, suffer from increased thrombotic complications, which seriously affect the prognosis of the patients.

  • Total EVs levels tend to increase after TAVR, especially TAVR with PCI, in 6 months, which positive correlation with the hypercoagulable state, and may lead to thrombosis.

  • EVs play the procoagulant role in patients after TAVR, especially TAVR with PCI.

  • Blockade of PS-positive EVs (PS+EVs) may improve the hypercoagulable state and reduce thrombotic complications in patients after TAVR.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Hu PP (2012) TAVR and SAVR: current treatment of aortic stenosis. Clin Med Insights Cardiol 6:125–139

    PubMed  PubMed Central  Google Scholar 

  2. Yutzey KE, Demer LL, Body SC et al (2014) Calcific aortic valve disease: a consensus summary from the Alliance of investigators on calcific aortic valve disease. Arterioscler Thromb Vasc Biol 34:2387–2393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cappabianca G, Ferrarese S, Musazzi A et al (2016) Predictive factors of long-term survival in the octogenarian undergoing surgical aortic valve replacement: 12-year single-centre follow-up. Heart Vessels 31:1798–1805

    Article  PubMed  Google Scholar 

  4. Mastoris I, Schoos MM, Dangas GD et al (2014) Stroke after transcatheter aortic valve replacement: incidence, risk factors, prognosis, and preventive strategies. Clin Cardiol 37:756–764

    Article  PubMed  PubMed Central  Google Scholar 

  5. Auffret V, Regueiro A, Trigo MD et al (2016) Predictors of early cerebrovascular events in patients with aortic stenosis undergoing transcatheter aortic valve replacement. J Am Coll Cardiol 68:673–684

    Article  PubMed  Google Scholar 

  6. Yanagisawa R, Hayashida K, Yamada Y et al (2016) Incidence, predictors, and mid-term outcomes of possible leaflet thrombosis after TAVR. JACC Cardiovasc Imaging

  7. Brouwer J, Nijenhuis VJ, Delewi R et al (2020) Aspirin with or without Clopidogrel after Transcatheter aortic-valve implantation. N Engl J Med 383:1447–1457

    Article  CAS  PubMed  Google Scholar 

  8. Nijenhuis VJ, Brouwer J, Delewi R et al (2020) Anticoagulation with or without Clopidogrel after Transcatheter aortic-valve implantation. N Engl J Med 382:1696–1707

    Article  CAS  PubMed  Google Scholar 

  9. Yeung T, Gilbert GE, Shi J et al (2008) Membrane phosphatidylserine regulates surface charge and protein localization. Science 319:210–213

    Article  CAS  PubMed  Google Scholar 

  10. Owens AP 3rd, Mackman N (2011) Microvesicles in hemostasis and thrombosis. Circ Res 108:1284–1297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mackman N, Tilley RE, Key NS (2007) Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol 27:1687–1693

    Article  CAS  PubMed  Google Scholar 

  12. Perez-Pujol S, Marker PH, Key NS (2007) Platelet microvesicles are heterogeneous and highly dependent on the activation mechanism: studies using a new digital flow cytometer. Cytometry A 71:38–45

    Article  PubMed  Google Scholar 

  13. Carroll JD, Mack MJ, Vemulapalli S et al (2020) STS-ACC TVT Registry of Transcatheter aortic valve replacement. J Am Coll Cardiol 76:2492–2516

    Article  CAS  PubMed  Google Scholar 

  14. Jung C, Lichtenauer M, Figulla H-R et al (2017) Microvesicles in patients undergoing transcatheter aortic valve implantation (TAVI). Heart Vessels 32:458–466

    Article  PubMed  Google Scholar 

  15. Zhou B, Li J, Chen S et al (2016) Time course of various cell origin circulating microvesicles in ST-segment elevation myocardial infarction patients undergoing percutaneous transluminal coronary intervention. Exp Ther Med 11:1481–1486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jung RG, Duchez A, Simard T et al (2022) Plasminogen activator inhibitor-1-Positive platelet-derived extracellular vesicles predicts MACE and the Proinflammatory SMC phenotype. JACC Basic Transl Sci 7:985–997

    Article  PubMed  PubMed Central  Google Scholar 

  17. Joseph J, Naqvi SY, Giri J et al (2017) Aortic stenosis: pathophysiology, diagnosis, and Therapy. Am J Med 130:253–263

    Article  PubMed  Google Scholar 

  18. Shi J, Heegaard CW, Rasmussen JT et al (2004) Lactadherin binds selectively to membranes containing phosphatidyl-L-serine and increased curvature. Biochim Biophys Acta 1667:82–90

    Article  CAS  PubMed  Google Scholar 

  19. Marchini JF, Miyakawa AA, Tarasoutchi F et al (2016) Endothelial, platelet, and macrophage microparticle levels do not change acutely following transcatheter aortic valve replacement. J Negat Results Biomed 15:7

    Article  PubMed  PubMed Central  Google Scholar 

  20. He Z, Si Y, Jiang T et al (2016) Phosphotidylserine exposure and neutrophil extracellular traps enhance procoagulant activity in patients with inflammatory bowel disease. Thromb Haemost 115:738–751

    Article  PubMed  Google Scholar 

  21. Horn P, Stern D, Veulemans V et al (2015) Improved endothelial function and decreased levels of endothelium-derived microvesicles after transcatheter aortic valve implantation. EuroIntervention 10:1456–1463

    Article  PubMed  Google Scholar 

  22. Petrov G, Regitz-Zagrosek V, Lehmkuhl E et al (2010) Regression of myocardial hypertrophy after aortic valve replacement: faster in women? Circulation 122:23–28

    Article  Google Scholar 

  23. Li J, Tong D, Chen F et al (2021) Inflammatory cytokines enhance procoagulant activity of platelets and endothelial cells through phosphatidylserine exposure in patients with essential hypertension. J Thromb Thrombolysis 51:933–940

    Article  CAS  PubMed  Google Scholar 

  24. Atmaca HU, Akbas F, Aral H (2019) Relationship between circulating microvesicles and hypertension and other cardiac disease biomarkers in the elderly. BMC Cardiovasc Disord 19:164

    Article  Google Scholar 

  25. Shaw AW, Pureza VS, Sligar SG et al (2007) The local phospholipid environment modulates the activation of blood clotting. J Biol Chem 282:6556–6563

    Article  CAS  PubMed  Google Scholar 

  26. Rao LVM, Kothari H, Pendurthi UR (2012) Tissue factor encryption and decryption: facts and controversies. Thromb Res 129:13–17

    Article  Google Scholar 

  27. Koganti S, Eleftheriou D, Gurung R et al (2021) Persistent circulating platelet and endothelial derived microparticle signature may explain on-going pro-thrombogenicity after acute coronary syndrome. Thromb Res 206:60–65

    Article  CAS  PubMed  Google Scholar 

  28. Biasucci LM, Porto I, Di Vito L et al (2012) Differences in microparticle release in patients with acute coronary syndrome and stable angina. Circ J 76:2174–2182

    Article  CAS  PubMed  Google Scholar 

  29. Lacroix R, Dignat-George F (2012) Microvesicles as a circulating source of procoagulant and fibrinolytic activities in the circulation. Thromb Res 129:27–29

    Article  Google Scholar 

  30. Lacroix R, Plawinski L, Robert S et al (2012) Leukocyte- and endothelial-derived microvesicles: a circulating source for fibrinolysis. Haematologica 97:1864–1872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Vion AC, Ramkhelawon B, Loyer X et al (2013) Shear stress regulates endothelial microparticle release. Circ Res 112:1323–1333

    Article  CAS  PubMed  Google Scholar 

  32. Nomura S, Tandon NN, Nakamura T et al (2001) High-shear-stress-induced activation of platelets and microvesicles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. Atherosclerosis 158:277–287

    Article  CAS  PubMed  Google Scholar 

  33. Nomura S, Komiyama Y (1997) Shear stress and platelet-derived microvesicles. Rinsho Byori 45:927–933

    CAS  PubMed  Google Scholar 

  34. Ding J, Chen Z, Niu S et al (2015) Quantification of Shear-Induced platelet activation: high shear stresses for short exposure time. Artif Organs 39:576–583

    Article  CAS  PubMed  Google Scholar 

  35. Giannella A, Ceolotto G, Radu CM et al (2021) PAR-4/Ca(2+)-calpain pathway activation stimulates platelet-derived microvesicles in hyperglycemic type 2 diabetes. Cardiovasc Diabetol 20:77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nomura S, Imamura A, Okuno M et al (2000) Platelet-derived microvesicles in patients with arteriosclerosis obliterans: enhancement of high shear-induced microparticle generation by cytokines. Thromb Res 98:257–268

    Article  CAS  PubMed  Google Scholar 

  37. Leroyer AS, Ebrahimian TG, Cochain C et al (2009) Microvesicles from ischemic muscle promotes postnatal vasculogenesis. Circulation 119:2808–2817

    Article  PubMed  Google Scholar 

  38. Karten B, Campenot RB, Vance DE et al (2006) Expression of ABCG1, but not ABCA1, correlates with cholesterol release by cerebellar astroglia. J Biol Chem 281:4049–4057

    Article  CAS  PubMed  Google Scholar 

  39. Komoriyama H, Kimiya K, Nagai T et al (2021) Blood flow dynamics with four-dimensional flow cardiovascular magnetic resonance in patients with aortic stenosis before and after transcatheter aortic valve replacement. J Cardiovasc Magn Reson 23:81

    Article  PubMed Central  Google Scholar 

  40. Leroyer AS, Isobe H, Leseche G et al (2007) Cellular origins and thrombogenic activity of microvesicles isolated from human atherosclerotic plaques. J Am Coll Cardiol 49:772–777

    Article  CAS  PubMed  Google Scholar 

  41. Viera AJ, Mooberry M, Key NS (2012) Microvesicles in cardiovascular disease pathophysiology and outcomes. J Am Soc Hypertens 6:243–252

    Article  CAS  PubMed  Google Scholar 

  42. Barthélémy O, Collet JP, Montalescot G (2016) Cerebral embolism: a silent iatrogenic complication of TAVR that needs voiced consideration. J Am Coll Cardiol 68:600–602

    Article  PubMed  Google Scholar 

  43. Nombela-Franco L, Webb JG, Jaegere PP et al (2012) Timing, predictive factors, and prognostic value of cerebrovascular events in a large cohort of patients undergoing transcatheter aortic valve implantation. Circulation 126:3041–3053

    Article  PubMed  Google Scholar 

  44. Ghanem A, Kocurek J, Sinning J-M et al (2013) Cognitive trajectory after transcatheter aortic valve implantation. Circ Cardiovasc Interv 6:615–624

    Article  PubMed  Google Scholar 

  45. Pache G, Schoechlin S, Blanke P et al (2016) Early hypo-attenuated leaflet thickening in balloon-expandable transcatheter aortic heart valves. Eur Heart J 37:2263–2271

    Article  PubMed  Google Scholar 

  46. Holmes DR Jr, Mack MJ, Kaul S et al (2012) 2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement. J Am Coll Cardiol 59:1200–1254

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank FX for blood sample collection; and JZ and DT for excellent technical assistance.

Funding

This study was supported by the Medical and Health Science and Technology Development Plan Project of Shandong Province (202003010399).

Author information

Authors and Affiliations

  1. Department of emergency, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

    Hang Chi

  2. Department of Cardiology, School of Medicine, Qingdao Municipal Hospital, Qingdao University, NO. 5 Donghai Middle Road, Qingdao, 266071, Shandong, China

    Yibing Shao, Fangyu Xie & Jihe Li

  3. Department of General Practice, People’s Hospital of Longhua, Shenzhen, China

    Jian Zhang

  4. Department of General Surgery, Qingdao FUWAI Cardiovascular Hospital, Qingdao, Shandong Province, China

    Guixin Zhang

  5. Department of Infectious Diseases, People’s Hospital of Longhua, Shenzhen, China

    Guihua Jiang

  6. Department of Oncology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, NO. 1 Jiaozhou Road, Qingdao, 266071, Shandong, China

    Dongxia Tong

Authors
  1. Hang Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yibing Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fangyu Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guixin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guihua Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dongxia Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jihe Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DT and JL conceived the study. HC, FX, GZ and JZ conducted the assays. GJ, YS and HC collected and analyzed the data, and made the tables and figures, wrote and retouch the manuscript. All authors approved the final manuscript.

Corresponding authors

Correspondence to Dongxia Tong or Jihe Li.

Ethics declarations

Conflict of interest

Authors, HC, YS, FX, GZ, JZ, GJ, DT and JL declare to 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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chi, H., Shao, Y., Xie, F. et al. Procoagulant effect of extracellular vesicles in patients after transcatheter aortic valve replacement or transcatheter aortic valve replacement with percutaneous coronary intervention. J Thromb Thrombolysis 56, 264–274 (2023). https://doi.org/10.1007/s11239-023-02835-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-023-02835-5

Keywords

Search

Navigation