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Structural Valve Deterioration Is Linked to Increased Immune Infiltrate and Chemokine Expression

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Abstract

We aim to investigate whether structural valve deterioration (SVD) of bioprosthetic xenogenic tissue heart valves (XTHVs) is associated with increased immune cell infiltration and whether co-expression of several chemokines correlates with this increase in immune infiltrate. Explanted XTHVs from patients undergoing redo valve replacement for SVD were obtained. Immunohistochemical, microscopic, and gene expression analysis approaches were used. XTHVs (n = 37) were obtained from 32 patients (mean 67.7 years) after a mean time of 11.6 years post-implantation. Significantly increased immune cellular infiltration was observed in the explanted SVD valves for all immune cell types examined, including T cells, macrophages, B cells, neutrophils, and plasma cells, compared to non-SVD controls. Furthermore, a significantly increased chemokine gradient in explanted SVD valves accompanied immune cell infiltration. These data suggest the development of SVD is associated with a significantly increased burden of immune cellular infiltrate correlated to the induction of a chemokine gradient around the XHTV, representing chronic immune rejection.

Graphical abstract

Proposed interaction between innate and adaptive immunity leading to the development of structural valve deterioration in xenogenic tissue heart valves.

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Abbreviations

FFPE:

Formalin-fixed, paraffin-embedded

H&E:

Hematoxylin and eosin

HPF:

High-powered field

RNA:

Ribonucleic acid

SVD:

Structural valve deterioration

VHD:

Valvular heart disease

XTHV:

Xenogenic tissue heart valve

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Funding

University Hospital Foundation, Edmonton, AB

Edmonton Civic Employees Charitable Assistance Fund, Edmonton, AB

Author information

Authors and Affiliations

  1. Division of Cardiac Surgery, Department of Surgery, University of Alberta, Edmonton, AB, T6G 2R3, Canada

    Sabin J. Bozso, Michael C. Moon, Darren H. Freed, Jayan Nagendran & Jeevan Nagendran

  2. Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, T6G 2R3, Canada

    Jimmy J.H. Kang

  3. Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, AB, T6G 2R3, Canada

    Ratnadeep Basu

  4. Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, T6G 2R3, Canada

    Benjamin Adam

  5. Cardiovascular Research Centre, Division of Pediatrics, University of Alberta, Edmonton, AB, T6G 2R3, Canada

    Jason R.B. Dyck

  6. Cardiovascular Research Centre, Division of Cardiology, University of Alberta, Edmonton, AB, T6G 2R3, Canada

    Gavin Y. Oudit

Authors
  1. Sabin J. Bozso
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  2. Jimmy J.H. Kang
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Correspondence to Jeevan Nagendran.

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The authors declare that they have no conflicts of interest.

Statement of Informed Consent

Patient and procedural data were collected from retrospective chart reviews. The Research Ethics Board at the University of Alberta approved the research protocol, including a waiver of individual consent.

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Associate Editor Adrian Chester oversaw the review of this article

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Bozso, S.J., Kang, J.J., Basu, R. et al. Structural Valve Deterioration Is Linked to Increased Immune Infiltrate and Chemokine Expression. J. of Cardiovasc. Trans. Res. 14, 503–512 (2021). https://doi.org/10.1007/s12265-020-10080-x

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  • DOI: https://doi.org/10.1007/s12265-020-10080-x

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