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Complement activation is involved in the structural deterioration of bovine pericardial bioprosthetic heart valves
1Centre de Recherches Chirurgicales, CNRS URA 1431, Association Claude Bernard, Service de Chirurgie Thoracique et Cardiovasculaire, Hopital Henri Mondor, Créteil, France.
Insights
Bioprosthetic valve deterioration involves immune responses. Immunoglobulins G (IgG) and complement proteins trigger inflammation, leading to matrix breakdown and valve failure. This highlights immune system involvement in bioprosthetic heart valve degradation.
Area of Science:
- Biomaterials Science
- Immunology
- Cardiovascular Research
Background:
- Bioprosthetic heart valves (BHVs) can fail due to matrix deterioration.
- Understanding molecular mechanisms of BHV degradation is crucial for developing durable valves.
- Morphologic features include disintegrated collagen and protein deposits in explanted valves.
Purpose of the Study:
- To investigate biologic factors contributing to bioprosthetic matrix degradation.
- To gather experimental evidence of immune system involvement in BHV failure.
- To elucidate the molecular pathways initiating bioprosthetic valve deterioration.
Main Methods:
- Explantation and analysis of clinically failed BHVs (Mitroflow, Hancock, Ionescu-Shiley, Sorin).
- Immunohistochemical staining with labeled antibodies to plasma proteins and cells.
- Immunoenzymic assay and Western blot analysis of valve extracts for fibrin peptides and complement breakdown products.
Main Results:
- Accumulation of Immunoglobulin G (IgG) and complement proteins (C1q, C3, C4) near dissociated collagen fibers.
- Identification of fibrin on the cuspal surface and in disrupted areas.
- Detection of fibrin peptides and complement activation products, indicating monocyte chemotaxis and potential activation of macrophages and neutrophil elastase.
Conclusions:
- Non-calcific deterioration of BHVs involves immune system activation.
- IgG aggregates trigger complement activation, generating signals for immune cell recruitment and matrix degradation.
- Cooperation between immune-mediated damage and mechanical stress contributes to the breakdown of the bioprosthetic matrix.
Abstract:
Disintegrated collagen fibers surrounded with protein deposits are a morphologic feature in torn, folded, and disrupted cusps of pericardial prostheses explanted for clinical dysfunction. New technologies for valve bioprostheses with improved durability require further investigation of molecular mechanisms initiating the deterioration of bioprosthetic valves. The authors' aim was to obtain experimental evidence of biologic factors contributing to the degradation of the bioprosthetic matrix. Clinically failed Mitroflow (22), Hancock (3), Ionescu-Shiley (2), and Sorin (1) valves were explanted after 69-170 months. Non calcific deterioration of the prosthetic matrix was studied with labeled antibodies to plasma proteins and cells. IgG, and complement proteins C1q, C3, and C4 were accumulated close to dissociated collagen bundles (26/28) throughout the prostheses. Fibrin was identified on the cuspal surface and in the deep disrupted areas. The fibrin peptides and proteolytic breakdown products of the complement components, the latter consistent with complement activation and chemotaxis for monocytes, were shown by immunoenzymic assay on Western blots from the valve extracts. The complement activation triggered by the IgG aggregates generates bioactive peptide signals that can activate macrophages (22/28) and neutrophil granulocyte elastase (22/24) able to cooperate with the mechanical stress in the breakdown of the chemically processed, non hemocompatible, and non-self macromolecular matrix.