Preview

Complex Issues of Cardiovascular Diseases

Advanced search

N-GLYCOLYLNEURAMINIC ACID AS A POSSIBLE TRIGGER FOR IMMUNE REJECTION OF EPOXY-TREATED XENO-PERICARDIAL HEART VALVE BIOPROSTHESES

https://doi.org/10.17802/2306-1278-2023-12-3-173-180

Abstract

Highlights

  • Stabilization of bovine pericardial tissue by ethylene glycol diglycidyl ether does not remove the N-glycolylneuraminic acid contained in its structure, which is one of the most immunoreactive glycan xenoantigens;
  • N-glycolylneuraminic acid can potentially cause early immune rejection of epoxy-treated bioprosthetic heart valves.

 

Aim. To assess the presence of N-glycolylneuraminic acid (Neu5Gc) in an intact bovine pericardial tissue stabilized by ethylene glycol diglycidyl ether and in the leaflets of epoxy-treated bioprosthetic heart valves (BHV) explanted due to dysfunction.

Methods. By means of immunochemistry (using anti-Neu5Gc antibodies), we studied the fragments of 5 samples of intact epoxy-treated bovine pericardium commonly used in cardiac surgery. Similarly, we examined the fragments of the leaflets of 8 epoxy-treated BHVs that lasted for different time periods (1 day to 68 months) and excised during reoperation. The native bovine pericardium and the leaflets of 3 human aortic valves (AV) removed during reoperation in patients with aortic stenosis were used as positive and negative controls, respectively.

Results. Positive reaction for Neu5Gc was observed in intact epoxy-treated xenopericardium and BHVs excised 1, 2, 20 and 42 days after implantation. The tissue of BHV that had lasted 30 months was characterized by the faint presence of Neu5Gc. In the leaflets of AV and in BHVs, explanted after 34, 63 and 68 months, Neu5Gc was not detected. 

Conclusion. Stabilization of xenobiomaterial with ethylene glycol diglycidyl ether does not remove the Neu5Gc. This saccharide remains in the biological tissue of epoxy-treated BHV for about 2.5 years after implantation. 

About the Authors

Alexander E. Kostyunin
Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”
Russian Federation

PhD, researcher at the Laboratory of New Biomaterials, Department of Experimental Medicine, Federal State Budgetary Institution «Research Institute for Complex Issues of Cardiovascular Diseases», Kemerovo, Russian Federation



Tatiana V. Glushkova
Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”
Russian Federation

PhD, senior researcher at the Laboratory of New Biomaterials, Department of Experimental Medicine, Federal State Budgetary Institution «Research Institute for Complex Issues of Cardiovascular Diseases», Kemerovo, Russian Federation



Maria A. Rezvova
Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”
Russian Federation

a junior research assistant at the Laboratory of New Biomaterials, the Department of Experimental Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russian Federation



Kirill Yu. Klyshnikov
Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”
Russian Federation

PhD, a research assistant at the Laboratory of New Biomaterials, the Department of Experimental Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russian Federation



Pavel S. Onishchenko
Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”
Russian Federation

a junior research assistant at the Laboratory of New Biomaterials, the Department of Experimental Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russian Federation



Evgeny A. Ovcharenko
Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”
Russian Federation

PhD, Head of the Laboratory of New Biomaterials, the Department of Experimental Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russian Federation



References

1. Timchenko T.P. Bisphosphonates as potential inhibitors of calcification in bioprosthetic heart valves (review). Modern Technologies in Medicine. 2022; 14(2):68-79. (in Russian) doi:10.17691/stm2022.14.2.07

2. Head S.J., Çelik M., Kappetein A.P. Mechanical versus bioprosthetic aortic valve replacement. Eur. Heart J. 2017; 38(28):2183-2191. doi:10.1093/eurheartj/ehx141

3. Fatima B., Mohananey D., Khan F.W., Jobanputra Y., Tummala R., Banerjee K. et al. Durability data for bioprosthetic surgical aortic valve: a systematic review. JAMA Cardiol. 2019; 4(1):71-80. doi:10.1001/jamacardio.2018.4045

4. Capodanno D., Petronio A.S., Prendergast B., Eltchaninoff H., Vahanian A., Modine T. et al. Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) endorsed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 2017; 38(45):3382-3390. doi:10.1093/eurheartj/ehx303

5. Dvir D., Bourguignon T., Otto C.M., Hahn R.T., Rosenhek R., Webb J.G. et al. Standardized definition of structural valve degeneration for surgical and transcatheter bioprosthetic aortic valves. Circulation. 2018; 137(4):388-399. doi:10.1161/CIRCULATIONAHA.117.030729

6. Bozso, S.J., Kang, J.J., Basu, R. Adam B., Dyck J.R.B., Oudit G.Y. et al. Structural valve deterioration is linked to increased immune infiltrate and chemokine expression. J Cardiovasc Trans Res. 2021; 14:503-512. doi:10.1007/s12265-020-10080-x

7. Bozso S.J., El-Andari R., Al-Adra D., Moon M.C., Freed D.H., Nagendran J. et al. A review of the immune response stimulated by xenogenic tissue heart valves. Scand J Immunol. 2021; 93(4):e13018. doi:10.1111/sji.13018

8. Senage T., Paul A., Le Tourneau T., Fellah-Hebia I., Vadori M., Bashir S. et al. The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration. Nat Med. 2022; 28(2):283-294. doi:10.1038/s41591-022-01682-w

9. Barone A., Benktander J., Whiddon C., Jin C., Galli C., Teneberg S. et al. Glycosphingolipids of porcine, bovine, and equine pericardia as potential immune targets in bioprosthetic heart valve grafts. Xenotransplantation. 2018; 25(5):e12406. doi:10.1111/xen.12406

10. Reuven E.M., Leviatan Ben-Arye S., Marshanski T., Breimer M.E., Yu H., Fellah-Hebia I. et al. Characterization of immunogenic Neu5Gc in bioprosthetic heart valves. Xenotransplantation. 2016; 23(5):381-92. doi:10.1111/xen.12260

11. Barbarash L.S., Zhuravleva I.Yu. Bioprosthetic heart valve evolution: two decades of advances and challenges. Complex Issues of Cardiovascular Diseases. 2012; 1:4-11. (in Russian) doi:10.17802/2306-1278-2012-1-4-11

12. Kostyunin A.E., Rezvova M.A. The role of residual xenoanthigens in the degeneration of xenogenic bioprosthetic heart valves. Immunologiya. 2019; 40(4):56-63. (in Russian) doi:10.24411/0206-4952-2019-14005

13. Altman M.O., Gagneux P. Absence of Neu5Gc and presence of anti-Neu5Gc antibodies in humans – an evolutionary perspective. Front Immunol. 2019; 10:789. doi: 10.3389/fimmu.2019.00789

14. Zhu A., Hurst R. Anti-N-glycolylneuraminic acid antibodies identified in healthy human serum. Xenotransplantation. 2002; 9(6):376-381. doi:10.1034/j.1399-3089.2002.02138.x

15. Marro M., Kossar A.P., Xue Y., Frasca A., Levy R.J., Ferrari G. Noncalcific mechanisms of bioprosthetic structural valve degeneration. J Am Heart Assoc. 2021; 10(3):e018921. doi:10.1161/JAHA.120.018921

16. Reuven E.M., Leviatan Ben-Arye S., Marshanski T., Breimer M.E., Yu H., Fellah-Hebia I. et al. Characterization of immunogenic Neu5Gc in bioprosthetic heart valves. Xenotransplantation. 2016; 23(5):381-92. doi:10.1111/xen.12260

17. Naso F., Gandaglia A., Bottio T., Tarzia V., Nottle M.B., d'Apice A.J. et al. First quantification of alpha-Gal epitope in current glutaraldehyde-fixed heart valve bioprostheses. Xenotransplantation. 2013; 20(4):252-261. doi:10.1111/xen.12044

18. Mukhamadiyarov R.A., Rutkovskaya N.V., Sidorova O.D., Barbarash L.S. Cellular composition of calcified bioprosthetic heart valves. Annals of the Russian Academy of Medical Sciences. 2015; 70(6):662-668. (in Russian) doi:10.15690/vramn560

19. Kostyunin A., Mukhamadiyarov R., Glushkova T., Bogdanov L., Shishkova D., Osyaev N. et al. Ultrastructural pathology of atherosclerosis, calcific aortic valve disease, and bioprosthetic heart valve degeneration: commonalities and differences. Int J Mol Sci. 2020; 21(20):7434. doi:10.3390/ijms21207434

20. Gates K.V., Xing Q., Griffiths L.G. Immunoproteomic identification of noncarbohydrate antigens eliciting graft-specific adaptive immune responses in patients with bovine pericardial bioprosthetic heart valves. Proteomics Clin. Appl. 2019; 13(4):e1800129. doi:10.1002/prca.201800129

21. Fournier P.E., Thuny F., Grisoli D., Lepidi H., Vitte J., Casalta J.P. et al. A deadly aversion to pork. Lancet. 2011; 377(9776):1542. doi:10.1016/S0140-6736(11)60021-4

22. Heuschkel M.A., Leitolis A., Roderjan J.G., Suss P.H., Luzia C.A.O., da Costa F.D.A. et al. In vitro evaluation of bovine pericardium after a soft decellularization approach for use in tissue engineering. Xenotransplantation. 2019; 26(2):e12464. doi:10.1111/xen.12464

23. Wu L.C., Kuo Y.J., Sun F.W., Chen C.H., Chiang C.J., Weng P.W. et al. Optimized decellularization protocol including α-Gal epitope reduction for fabrication of an acellular porcine annulus fibrosus scaffold. Cell Tissue Bank. 2017; 18(3):383-396. doi:10.1007/s10561-017-9619-4


Supplementary files

Review

For citations:


Kostyunin A.E., Glushkova T.V., Rezvova M.A., Klyshnikov K.Yu., Onishchenko P.S., Ovcharenko E.A. N-GLYCOLYLNEURAMINIC ACID AS A POSSIBLE TRIGGER FOR IMMUNE REJECTION OF EPOXY-TREATED XENO-PERICARDIAL HEART VALVE BIOPROSTHESES. Complex Issues of Cardiovascular Diseases. 2023;12(3):173-180. (In Russ.) https://doi.org/10.17802/2306-1278-2023-12-3-173-180

Views: 326


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2306-1278 (Print)
ISSN 2587-9537 (Online)