Characterization of the cellular infiltrate in bioprosthetic heart valves explanted from patients with structural valve deterioration

Manji, Rizwan A.; Hara, Hidetaka; Cooper, David K. C.

doi:10.1111/xen.12187

Cited by 16 publications

(16 citation statements)

References 16 publications

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“…The alternate hypothesis for the finding of lower anti‐carbohydrate antibody presence in GFBP valve recipients is that these patients downregulate production of these natural antibodies. It has been previously demonstrated that even after the fixation process, α‐Gal epitopes are available on GFBP valve surfaces, although explanted valves lack anti‐α‐Gal antibody deposition . A potential explanation for this previously reported contradictory finding could be that following GFBP valve implantation, patients downregulate anti‐α‐Gal antibody production.…”

Section: Discussionmentioning

confidence: 97%

“…Furthermore, valves explanted from human patients with SVD have shown deposition of IgG antibodies, which is independent of α‐gal . Antibody deposition has been implicated in leaflet calcification and macrophage infiltration leading to SVD and ultimately valve failure . Finally, previous publications have demonstrated that glutaraldehyde‐fixed tissue generates a robust antigen‐specific antibody response .…”

Section: Introductionmentioning

confidence: 99%

“…Recent advances in immunoproteomic antigen identification, applied to animal models, have demonstrated presence of non‐gal antigenic proteins in all subcellular tissue locations of candidate unfixed xenogeneic biomaterials such as BP . Furthermore, valves explanted from human patients with SVD have shown deposition of IgG antibodies, which is independent of α‐gal . Antibody deposition has been implicated in leaflet calcification and macrophage infiltration leading to SVD and ultimately valve failure .…”

Section: Introductionmentioning

confidence: 99%

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Immunoproteomic Identification of Noncarbohydrate Antigens Eliciting Graft‐Specific Adaptive Immune Responses in Patients with Bovine Pericardial Bioprosthetic Heart Valves

Gates

Xing

Griffiths

2018

Proteomics Clinical Apps

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Purpose: This case-control retrospective discovery study is to identify antigenic bovine pericardium (BP) proteins that stimulate graft-specific humoral immune response in patients implanted with glutaraldehyde fixed bovine pericardial (GFBP) heart valves. Experimental design: Banked serum is collected from age-and sex-matched patients who received either a GFBP or mechanical heart valve replacement. Serum IgG is isolated and used to generate poly-polyclonal antibody affinity chromatography columns from each patient. Native and deglycosylated BP protein extracts are separately added to individual patient affinity chromatography columns, with unbound proteins washed through the column. Proteins captured in the affinity chromatography columns are submitted for proteomic identification. Differences between GFBP and mechanical heart valve replacement recipients are analyzed with Gaussian linearized modeling. Results: Carbohydrate antigens overwhelm protein capture in the column, requiring BP protein deglycosylation prior to affinity chromatography. Nineteen BP protein antigens, which stimulated graft-specific IgG production, are identified in patients who received GFBP valve replacements. Identified antigens are significantly over-represented for calcium-binding proteins. Conclusions and clinical relevance: Patients implanted with GFBP valves develop a graft-specific humoral immune response toward BP protein antigens, with 19 specific antigens identified in this work. The molecular functions of over-represented antigens, specifically calcium-binding proteins, may aid in understanding the underlying factors that contribute to structural valve deterioration.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immunoproteomic Identification of Noncarbohydrate Antigens Eliciting Graft‐Specific Adaptive Immune Responses in Patients with Bovine Pericardial Bioprosthetic Heart Valves

Gates

Xing

Griffiths

2018

Proteomics Clinical Apps

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“…167 Similarly, GTA-fixed heart valves explanted due to development of structural valve deterioration have been shown to be universally positive for non-a-Gal IgG presence. 89,168 GTA fixation is also associated with alterations in ECM scaffold mechanical properties and renders the resultant biomaterial prone to calcification due to free aldehyde residues in the resultant tissue. 169 As previously discussed, the specific limitations of GTA fixation are likely to be particularly detrimental in vascular tissues since they coincide with known failure mechanisms of small diameter vascular grafts.…”

Section: Overcoming Failure Mechanisms In Vascular Ecm Scaffoldsmentioning

confidence: 99%

Small Diameter Xenogeneic Extracellular Matrix Scaffolds for Vascular Applications

Higuita

Griffiths

2020

Tissue Engineering Part B: Reviews

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Currently, despite the success of percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) remains among the most commonly performed cardiac surgical procedures in the United States. Unfortunately, the use of autologous grafts in CABG presents a major clinical challenge as complications due to autologous vessel harvest and limited vessel availability pose a significant setback in the success rate of CABG surgeries. Acellular extracellular matrix (ECM) scaffolds derived from xenogeneic vascular tissues have the potential to overcome these challenges, as they offer unlimited availability and sufficient length to serve as ''off-the-shelf'' CABGs. Unfortunately, regardless of numerous efforts to produce a fully functional small diameter xenogeneic ECM scaffold, the combination of factors required to overcome all failure mechanisms in a single graft remains elusive. This article covers the major failure mechanisms of current xenogeneic small diameter vessel ECM scaffolds, and reviews the recent advances in the field to overcome these failure mechanisms and ultimately develop a small diameter ECM xenogeneic scaffold for CABG.

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“…Determining the cause of SVD, and subsequent therapeutic targets to mitigate its development, has proven to be a significant challenge. Several studies have hypothesized that SVD is a chronic, immune‐mediated rejection process against the foreign xenogenic‐derived bioprosthetic valve . This hypothesis was further strengthened when it was identified that calcific degeneration of bioprosthetic valves was decreased by concomitant steroid use, possibly related to its immunosuppressive effects…”

Section: Introductionmentioning

confidence: 99%

Outcomes following bioprosthetic valve replacement in prior non‐cardiac transplant recipients

Bozso

Kang

Al‐Adra

et al. 2019

Clinical Transplantation

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Background We report on overall survival and valve‐related outcomes after bioprosthetic valve replacement in prior transplant recipients. Methods From January 2004 to December 2018, 20 consecutive patients (mean age 65.7‐years, 90% male) with prior non‐cardiac transplantation underwent bioprosthetic aortic (n = 18) or combined aortic and mitral (n = 2) valve replacement. Patients consisted of kidney (n = 14), lung (n = 2), liver (n = 3), and bone‐marrow (n = 2) transplants with the most common indication for valve replacement being calcific degeneration (n = 12). Outcomes were measured over a 12‐year span, with a median follow‐up duration of 3.9 years. Results Overall survival at 30 days was 100% and at median follow‐up was 60%. Acute kidney injury occurred in 50% (n = 10) with temporary dialysis required in 5% (n = 1) and 15% (n = 3) suffered respiratory failure. No patients experienced major bleeding, heart failure, or sternal wound infection. No patients required redo valve replacement during the study period. Conclusions Our results provide contemporary data demonstrating that patients with prior transplant can undergo bioprosthetic valve replacement with acceptable inhospital mortality rates and long‐term survival, with a low rate of major morbidity. Furthermore, bioprosthetic valve replacement is a viable option in this group of patients with no redo valve replacement and acceptable long‐term hemodynamic valvular function.

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Characterization of the cellular infiltrate in bioprosthetic heart valves explanted from patients with structural valve deterioration

Cited by 16 publications

References 16 publications

Immunoproteomic Identification of Noncarbohydrate Antigens Eliciting Graft‐Specific Adaptive Immune Responses in Patients with Bovine Pericardial Bioprosthetic Heart Valves

Immunoproteomic Identification of Noncarbohydrate Antigens Eliciting Graft‐Specific Adaptive Immune Responses in Patients with Bovine Pericardial Bioprosthetic Heart Valves

Small Diameter Xenogeneic Extracellular Matrix Scaffolds for Vascular Applications

Outcomes following bioprosthetic valve replacement in prior non‐cardiac transplant recipients

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