Skip to main content

Advertisement

Log in

Tirofiban Positively Regulates β1 Integrin and Favours Endothelial Cell Growth on Polylactic Acid Biopolymer Vascular Scaffold (BVS)

  • Original Article
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

An unexpectedly high incidence of thrombosis in patients that received the polylactic acid bioresorbable vascular scaffold (BVS) suggests a delayed/incomplete endothelial repair with this stent. The anti-platelet agent tirofiban stimulates endothelial cell migration and proliferation, mediated by VEGF production. We investigated the tirofiban effect on the migration and adhesion of endothelial cells to BVS, in vitro. We performed human umbilical endothelial cell (HUVEC) cultures in the presence of BVS. Tirofiban, similarly to VEGF, increased the ability of HUVEC to grow on the vascular scaffold, compared to unstimulated or abciximab-treated cells. Tirofiban increased HUVEC expression of β1 and β3 integrins along with collagen and fibronectin. A role for β1 integrin in the “pro-adhesive and -migratory” signals elicited by tirofiban was suggested by use of an anti-β1-blocking antibody that prevented poly-levo-lactic acid vascular scaffold colonization. Our study suggests that tirofiban may improve the outcomes of patients receiving BVS by accelerating stent endothelization.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Tenekecioglu, E., Farooq, V., Bourantas, C. V., et al. (2016). Bioresorbable scaffolds: a new paradigm in percutaneous coronary intervention. BMC Cardiovascular Disorders, 16, 38. https://doi.org/10.1186/s12872-016-0207-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Gogas, B. D. (2014). Bioresorbable scaffolds for percutaneous coronary interventions. Global Cardiology Science and Practice, 4, 409–427. Review. https://doi.org/10.5339/gcsp.2014.55.

    Article  Google Scholar 

  3. Brugaletta, S., Heo, J. H., Garcia-Garcia, H. M., et al. (2012). Endothelial-dependent vasomotion in a coronary segment treated by ABSORB everolimus-eluting bioresorbable vascular scaffold system is related to plaque composition at the time of bioresorption of the polymer: Indirect finding of vascular reparative therapy. European Heart Journal, 33, 1325–1333. https://doi.org/10.1093/eurheartj/ehr466.

    Article  PubMed  CAS  Google Scholar 

  4. Räber, L., Brugaletta, S., Yamaji, K., et al. (2015). Very late scaffold thrombosis intracoronary imaging and histopathological and spectroscopic findings. Journal of the American College of Cardiology, 66, 1901–1914. https://doi.org/10.1016/j.jacc.2015.08.853.

    Article  PubMed  CAS  Google Scholar 

  5. Hiltrop, N., Jorge, C., Bennett, J., et al. (2016). Late neoatherosclerotic scaffold failure: an unexpected Achilles heel for current bioresorbable scaffold technology? International Journal of Cardiology, 223, 133–135. https://doi.org/10.1016/j.ijcard.2016.08.076.

    Article  PubMed  Google Scholar 

  6. Lau, A. K., Leichtweis, S. B., Hume, P., et al. (2003). Probucol promotes functional reendothelialization in balloon-injured rabbit aortas. Circulation, 107, 2031–2036. https://doi.org/10.1161/01.CIR.0000062682.40051.43.

    Article  PubMed  CAS  Google Scholar 

  7. Wu, X., Zhao, Y., Tang, C., et al. (2016). Re-Endothelialization study on endovascular stents seeded by endothelial cells through up- or downregulation of VEGF. ACS Applied Materials & Interfaces, 8, 7578–7589. https://doi.org/10.1021/acsami.6b00152.

    Article  CAS  Google Scholar 

  8. Windecker, S., Kolh, P., Alfonso, F., et al. (2014). European Heart Journal, 35, 2541–2619. ESC/EACTS guidelines on myocardial revascularization: the task force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). https://doi.org/10.1093/eurheartj/ehu278.

    Article  PubMed  Google Scholar 

  9. Heestermans, A. A., Van Werkum, J. W., Hamm, C., et al. (2009). Marked reduction of early stent thrombosis with pre-hospital initiation of high-dose Tirofiban in ST-segment elevation myocardial infarction. Journal of Thrombosis and Haemostasis, 7, 1612–1618. https://doi.org/10.1111/j.1538-7836.2009.03573.x.

    Article  PubMed  CAS  Google Scholar 

  10. Giordano, A., D'Angelillo, A., Romano, S., et al. (2014). Tirofiban induces VEGF production and stimulates migration and proliferation of endothelial cells. Vascular Pharmacology, 61, 63–71. https://doi.org/10.1016/j.vph.2014.04.002.

    Article  PubMed  CAS  Google Scholar 

  11. Fonsatti, E., Sigalotti, L., Arslan, P., et al. (2003). Emerging role of endoglin (CD105) as a marker of angiogenesis with clinical potential in human malignancies. Current Cancer Drug Targets, 3, 427–432. https://doi.org/10.2174/1568009033481741.

    Article  PubMed  CAS  Google Scholar 

  12. Reinhart-King, C. A. (2008). Endothelial cell adhesion and migration. Methods in Enzymology, 443, 45–64. https://doi.org/10.1016/S0076-6879(08)02003-X.

    Article  PubMed  CAS  Google Scholar 

  13. Massé, J. M., Perlemuter, K., Debili, N., et al. (1999). Intracellular trafficking of the alphaIIbbeta3 receptor antagonist, abciximab, in normal and Glanzmann’s disease megakaryocytes. British Journal of Haematology, 107, 720–730. https://doi.org/10.1046/j.1365-2141.1999.01768.x.

    Article  PubMed  Google Scholar 

  14. Fässler, R., Pfaff, M., Murphy, J., et al. (1995). Lack of beta 1 integrin gene in embryonic stem cells affects morphology, adhesion, and migration but not integration into the inner cell mass of blastocysts. The Journal of Cell Biology, 128, 979–988. https://doi.org/10.1083/jcb.128.5.979.

    Article  PubMed  Google Scholar 

  15. Giampietro, C., Taddei, A., Corada, M., et al. (2012). Overlapping and divergent signaling pathways of N-cadherin and VE-cadherin in endothelial cells. Blood, 119, 2159–2170. https://doi.org/10.1182/blood-2011-09-381012.

    Article  PubMed  CAS  Google Scholar 

  16. Gao, H., Zhang, J., Liu, T., et al. (2011). Rapamycin prevents endothelial cell migration by inhibiting the endothelial-to-mesenchymal transition and matrix metalloproteinase-2 and -9: an in vitro study. Molecular Vision, 17, 3406–3414.

    PubMed  PubMed Central  CAS  Google Scholar 

  17. Xia, Y., Boey, F., & Venkatraman, S. S. (2010). Surface modification of poly (L-lactic acid) with biomolecules to promote endothelialization. Biointerphases, 5, FA32–FA40. https://doi.org/10.1116/1.3467508.

    Article  PubMed  Google Scholar 

  18. Bautch, V. L. (2017). Endoglin moves and shapes endothelial cells. Nature Cell Biology, 19, 593–595. https://doi.org/10.1038/ncb3543.

    Article  PubMed  CAS  Google Scholar 

  19. Rossi, E., Smadja, D. M., Boscolo, E., et al. (2016). Endoglin regulates mural cell adhesion in the circulatory system. Cellular and Molecular Life Sciences, 73, 1715–1739. https://doi.org/10.1007/s00018-015-2099-4.

    Article  PubMed  CAS  Google Scholar 

  20. Huttenlocher, A., & Horwitz, A. R. (2011). Integrins in cell migration. Cold Spring Harbor Perspectives in Biology, 3, a005074. https://doi.org/10.1101/cshperspect.a005074.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Lamouille, S., Xu, J., & Derynck, R. (2014). Molecular mechanisms of epithelial-mesenchymal transition. Nature Reviews. Molecular Cell Biology, 15, 178–196. https://doi.org/10.1038/nrm3758.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Jin, Y., Muhl, L., Burmakin, M., Wang, Y., Duchez, A. C., Betsholtz, C., Arthur, H. M., & Jakobsson, L. (2017). Endoglin prevents vascular malformation by regulating flow-induced cell migration and specification through VEGFR2 signalling. Nature Cell Biology, 19, 639–652. https://doi.org/10.1038/ncb3534.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Cox, E. A., Sastry, S. K., & Huttenlocher, A. (2001). Integrin-mediated adhesion regulates cell polarity and membrane protrusion through the rho family of GTPases. Molecular Biology of the Cell, 12, 265–277. https://doi.org/10.1091/mbc.12.2.265.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Butler, J. M., Kobayashi, H., & Rafii, S. (2010). Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors. Nature Reviews. Cancer, 10, 138–146. https://doi.org/10.1038/nrc2791.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Raynaud, C. M., Butler, J. M., Halabi, N. M., Ahmad, F. S., Ahmed, B., Rafii, S., & Rafii, A. (2013). Endothelial cells provide a niche for placental hematopoietic stem/progenitor cell expansion through broad transcriptomic modification. Stem Cell Research, 11, 1074–1090. https://doi.org/10.1016/j.scr.2013.07.010.

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

We thank Cardiovascular Service for supporting our research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maria Fiammetta Romano.

Ethics declarations

Conflict of Interest

Arturo Giordano is a consultant for Medtronic and Abbot; Simona Romano declares that she has no conflict of interest; Nicola Corcione declares that he has no conflict of interest; Giacomo Frati declares that he has no conflict of interest; Giuseppe Biondi Zoccai has consulted for Bayer and Abbot Vascular; Paolo Ferraro and Stefano Messina declares that they have no conflict of interest; Stefano Ottolini is a consultant for Correvio Italia, Cardiome Sarl; Maria Fiammetta Romano declares that she has no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Associate Editor Adrian Chester oversaw the review of this article

Electronic supplementary material

ESM 1

(PDF 162 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giordano, A., Romano, S., Corcione, N. et al. Tirofiban Positively Regulates β1 Integrin and Favours Endothelial Cell Growth on Polylactic Acid Biopolymer Vascular Scaffold (BVS). J. of Cardiovasc. Trans. Res. 11, 201–209 (2018). https://doi.org/10.1007/s12265-018-9805-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-018-9805-1

Keywords

Navigation