ArticleNature medicine2022
The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration.
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Article in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52citing papers in PubMed
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Who cites it
52 citing papers in PubMed, 92 citations in OpenAlex.
- Alpha-gal xenoantigens in bioprosthetic valve recipients: clinical implications for bioprosthesis longevity.Journal of cardiothoracic surgery · 2026Review
- The choice of mitral valve surgery type and mid-term outcomes in patients up to 70 years of age: Results of the AUTHEARTVISIT study.JTCVS open · 2026Article
- Dual itaconate delivery systems modulate macrophage Acod1-Hif-1α-glycolysis axis for immunotherapy of bioprosthetic heart valve calcification.Bioactive materials · 2026Article
- Quantification of Alpha-Gal Expression in Commercial BioProsthetic Heart Valves and Its Potential Mitigation.Structural heart : the journal of the Heart Team · 2026Article
- A looming wave of bioprosthetic transcatheter valve failure?-rethinking lifetime management and reintervention in aortic stenosis.Journal of visualized surgery · 2026Article
- Bioprosthetic heart valve degeneration: new insights into structural remodeling and calcification.Frontiers in cardiovascular medicine · 2026Review
- Preparation and evaluation of a small-diameter vascular graft with dual anticoagulant and anticalcification functions.Regenerative biomaterials · 2026Article
- Humoral immune responses to hyaluronan oligosaccharides in patients undergoing prosthetic valve surgery.Frontiers in immunology · 2026Article
- VITTA TRIAL - safety and performance at 3-year follow-up after implantation of the VIVERE® aortic bioprosthesis.Frontiers in cardiovascular medicine · 2026Article
- Antibody and Cellular Immune Responses in Old α1,3-Galactosyltransferase-Knockout Mice Implanted with Bioprosthetic Heart Valve Tissues.Bioengineering (Basel, Switzerland) · 2025Article
- [Research progress on calcification mechanism and anti-calcification strategies of vascular grafts].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2025Review
- Effects of a Drying Treatment on the Mechanical Properties and Hemodynamic Characteristics of Bovine Pericardial Bioprosthetic Valves.Journal of functional biomaterials · 2025Article
- Enhanced Detection of αGal Using a Novel Monoclonal IgG1 Antibody: Comparative Evaluation with IgM Antibody [Clone M86].Journal of personalized medicine · 2025Article
- Ectopic Calcification in Congenital Heart Surgery: A Material-Centric Review.Pediatric cardiology · 2025Review
- Pediatric partial heart xenotransplantation as an early use case of xenograft tissue.Future cardiology · 2025Review
- Transcatheter Aortic Valve Durability: Focus on Structural Valve Deterioration.Journal of the American Heart Association · 2025Review
- The choice of surgical aortic valve replacement type and mid-term outcomes in 50 to 65-year-olds: results of the AUTHEARTVISIT study.European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery · 2025Article
- Porcine pericardium crosslinked with POSS-PEG-CHO possesses weakened immunogenicity and anti-calcification property.Materials today. Bio · 2025Article
- IgG to Galactose-Alpha-1,3-Galactose: Impact of Alpha-Gal IgE Sensitization, Blood Type, and Tick Bites.Antibodies (Basel, Switzerland) · 2025Article
- Mechanistic Insights into Bioprosthetic Heart Valve Calcification and Anti-Calcification Strategies.Reviews in cardiovascular medicine · 2025Review
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Authors and funding
52 authors at 18 institutions in 9 countries.
Thomas Senage *Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.
Anu Paul *Department of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.ORCID http://orcid.org/0000-0003-2479-8398
Thierry Le Tourneau *Institut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.
Imen Fellah-HebiaInstitut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.
Marta VadoriConsortium for Research in Organ Transplantation, Ospedale Giustinianeo, Padova, Italy.
Salam BashirDepartment of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Manuel GaliñanesDepartment of Cardiac Surgery and Reparative Therapy of the Heart, Vall d'Hebron Research Institute, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Tomaso BottioCardiovascular Regenerative Medicine Group, Department of Cardiac, Thoracic and Vascular Surgery, University of Padova, Padova, Italy.ORCID http://orcid.org/0000-0001-7299-2983
Gino GerosaDepartment of Cardiac, Vascular and Thoracic Sciences and Public Health University of Padova, L.I.F.E.L.A.B. Program Veneto Region, Padova, Italy.
Arturo EvangelistaDepartment of Cardiology, Vall d'Hebron Research Institut, Hospital Vall d'Hebron, Barcelona, Spain.
Luigi P BadanoDepartment of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
Alberto NassiTransplantation Immunology Unit, Padova University Hospital, Padova, Italy.
Cristina CostaInfectious Diseases and Transplantation Division, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.ORCID http://orcid.org/0000-0002-1837-4268
Galli CesareAvantea, Cremona, Italy.ORCID http://orcid.org/0000-0002-9529-6136
Rizwan A ManjiDepartment of Surgery, Max Rady College of Medicine, University of Manitoba Cardiac Sciences Program, St Boniface Hospital, Winnipeg, Manitoba, Canada.ORCID http://orcid.org/0000-0002-5359-7889
Caroline Cueff de MonchyInstitut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.
Nicolas PiriouInstitut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.
Romain CapouladeInstitut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.
Jean-Michel SerfatyInstitut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.
Guillaume GuimbretièreInstitut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.
Etienne DantanInstitut National de la Santé et de la Recherche Médicale UMR 1246-SPHERE, Nantes University, Tours University, Nantes, France.ORCID http://orcid.org/0000-0001-7137-5051
Alejandro Ruiz-MajoralDepartment of Cardiology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.ORCID http://orcid.org/0000-0003-1836-5078
Guénola Coste du FouInstitut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France.
Shani Leviatan Ben-AryeDepartment of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Liana GovaniDepartment of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Sharon YehudaDepartment of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.ORCID http://orcid.org/0000-0003-2826-1061
Shirley Bachar AbramovitchDepartment of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Ron AmonDepartment of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Eliran Moshe ReuvenDepartment of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Yafit Atiya-NasagiDepartment of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Hai YuDepartment of Chemistry, University of California, Davis, Davis, CA, USA.ORCID http://orcid.org/0000-0002-4378-0532
Laura IopCardiovascular Regenerative Medicine Group, Department of Cardiac, Thoracic and Vascular Surgery, University of Padova, Padova, Italy.
Kelly CasósDepartment of Cardiac Surgery and Reparative Therapy of the Heart, Vall d'Hebron Research Institute, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Sebastián G KuguelInfectious Diseases and Transplantation Division, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.ORCID http://orcid.org/0000-0001-7213-6503
Arnau Blasco-LucasDepartment of Cardiac Surgery and Reparative Therapy of the Heart, Vall d'Hebron Research Institute, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID http://orcid.org/0000-0002-2796-7428
Eduard PermanyerDepartment of Cardiac Surgery and Reparative Therapy of the Heart, Vall d'Hebron Research Institute, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Fabrizio SbragaCardiac Surgery Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.
Roger LlatjósPathology Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.
Gabriel Moreno-GonzalezInfectious Diseases and Transplantation Division, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Melchor Sánchez-MartínezMind the Byte, Barcelona, Spain.ORCID http://orcid.org/0000-0002-3674-8577
Michael E BreimerDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Jan HolgerssonInstitute of Biomedicine, Department of Laboratory Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Susann TenebergInstitute of Biomedicine, Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Marta Pascual-GilabertInstitut Universitari de Ciència i Tecnologia (Inkemia Group), Barcelona, Spain.
Alfons Nonell-CanalsMind the Byte, Barcelona, Spain.
Yasuhiro TakeuchiDivision of Infection and Immunity, University College London, London, UK.
Xi ChenDepartment of Chemistry, University of California, Davis, Davis, CA, USA.ORCID http://orcid.org/0000-0002-3160-614X
Rafael MañezInfectious Diseases and Transplantation Division, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. rmanez@bellvitgehospital.cat.ORCID http://orcid.org/0000-0002-0884-5564
Jean-Christian RousselInstitut du Thorax, Institut National de la Santé et de la Recherche Médicale UMR1087, University Hospital, Nantes, France. jeanchristian.roussel@chu-nantes.fr.ORCID http://orcid.org/0000-0003-3928-6977
Jean-Paul SoulillouInstitut de Transplantation-Urologie-Néphrologie, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1064, Centre Hospitalier Universitaire de Nantes, Nantes, France. jean-paul.soulillou@univ-nantes.fr.ORCID http://orcid.org/0000-0001-7468-5135
Emanuele CozziTransplantation Immunology Unit, Padova University Hospital, Padova, Italy. emanuele.cozzi@unipd.it.ORCID http://orcid.org/0000-0001-7855-5055
Vered Padler-KaravaniDepartment of Cell Research and Immunology, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. vkaravani@tauex.tau.ac.il.ORCID http://orcid.org/0000-0002-4761-3571
Inserm · FRTel Aviv University · ILBellvitge University Hospital · ESUniversity of Padua · ITUniversitat Autònoma de Barcelona · ESUniversity of Gothenburg · SEInstitut d'Investigació Biomédica de Bellvitge · ESUniversité de Tours · FRUniversity of California, Davis · USAvantea · ITBrigham and Women's Hospital · USHebron University · PSInstitut Universitari de Ciencia i Tecnologia (Spain) · ESIRCCS Istituto Auxologico Italiano · ITIsrael Institute for Biological Research · ILSt. Boniface Hospital · CAUniversity College London · GBVall d'Hebron Institut de Recerca · ES
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-αGal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-αGal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack αGal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in αGal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability.
Indexed as
BioprosthesisGalactoseAnimalsAntibody FormationAortic ValveAortic Valve StenosisCalcinosisHumansImmunoglobulin GMicePolysaccharidesProspective StudiesGalactoseImmunoglobulin GPolysaccharides
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