TY - JOUR
T1 - Differential Immune Response to Bioprosthetic Heart Valve Tissues in the α1,3Galactosyltransferase-Knockout Mouse Model
AU - Casós, Kelly
AU - Llatjós, Roger
AU - Blasco-Lucas, Arnau
AU - Kuguel, Sebastián G.
AU - Sbraga, Fabrizio
AU - Galli, Cesare
AU - Padler-Karavani, Vered
AU - Le Tourneau, Thierry
AU - Vadori, Marta
AU - Perota, Andrea
AU - Roussel, Jean Christian
AU - Bottio, Tomaso
AU - Cozzi, Emanuele
AU - Soulillou, Jean Paul
AU - Galiñanes, Manuel
AU - Máñez, Rafael
AU - Costa, Cristina
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/7
Y1 - 2023/7
N2 - Structural valve deterioration (SVD) of bioprosthetic heart valves (BHVs) has great clinical and economic consequences. Notably, immunity against BHVs plays a major role in SVD, especially when implanted in young and middle-aged patients. However, the complex pathogenesis of SVD remains to be fully characterized, and analyses of commercial BHVs in standardized-preclinical settings are needed for further advancement. Here, we studied the immune response to commercial BHV tissue of bovine, porcine, and equine origin after subcutaneous implantation into adult α1,3-galactosyltransferase-knockout (Gal KO) mice. The levels of serum anti-galactose α1,3-galactose (Gal) and -non-Gal IgM and IgG antibodies were determined up to 2 months post-implantation. Based on histological analyses, all BHV tissues studied triggered distinct infiltrating cellular immune responses that related to tissue degeneration. Increased anti-Gal antibody levels were found in serum after ATS 3f and Freedom/Solo implantation but not for Crown or Hancock II grafts. Overall, there were no correlations between cellular-immunity scores and post-implantation antibodies, suggesting these are independent factors differentially affecting the outcome of distinct commercial BHVs. These findings provide further insights into the understanding of SVD immunopathogenesis and highlight the need to evaluate immune responses as a confounding factor.
AB - Structural valve deterioration (SVD) of bioprosthetic heart valves (BHVs) has great clinical and economic consequences. Notably, immunity against BHVs plays a major role in SVD, especially when implanted in young and middle-aged patients. However, the complex pathogenesis of SVD remains to be fully characterized, and analyses of commercial BHVs in standardized-preclinical settings are needed for further advancement. Here, we studied the immune response to commercial BHV tissue of bovine, porcine, and equine origin after subcutaneous implantation into adult α1,3-galactosyltransferase-knockout (Gal KO) mice. The levels of serum anti-galactose α1,3-galactose (Gal) and -non-Gal IgM and IgG antibodies were determined up to 2 months post-implantation. Based on histological analyses, all BHV tissues studied triggered distinct infiltrating cellular immune responses that related to tissue degeneration. Increased anti-Gal antibody levels were found in serum after ATS 3f and Freedom/Solo implantation but not for Crown or Hancock II grafts. Overall, there were no correlations between cellular-immunity scores and post-implantation antibodies, suggesting these are independent factors differentially affecting the outcome of distinct commercial BHVs. These findings provide further insights into the understanding of SVD immunopathogenesis and highlight the need to evaluate immune responses as a confounding factor.
KW - anti-Gal antibodies
KW - bioprosthetic heart valves
KW - cellular immune infiltrate
KW - structural valve deterioration
KW - α1,3-galactosyltransferase-knockout mice
UR - http://www.scopus.com/inward/record.url?scp=85166315286&partnerID=8YFLogxK
U2 - 10.3390/bioengineering10070833
DO - 10.3390/bioengineering10070833
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C2 - 37508860
AN - SCOPUS:85166315286
SN - 2306-5354
VL - 10
JO - Bioengineering
JF - Bioengineering
IS - 7
M1 - 833
ER -