Complement activation is involved in the structural deterioration of bovine pericardial bioprosthetic heart valves.
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.
Moczar
M
M
Centre de Recherches Chirurgicales, CNRS URA 1431, Association Claude Bernard, Service de Chirurgie Thoracique et Cardiovasculaire, Hopital Henri Mondor, Créteil, France.
Lecerf
L
L
Ginat
M
M
Loisance
D
D
D000328:Adult; D000368:Aged; D000818:Animals; D001705:Bioprosthesis / Q000009:adverse effects*; D002417:Cattle; D003094:Collagen / Q000378:metabolism; D003167:Complement Activation; D006350:Heart Valve Prosthesis / Q000009:adverse effects*; D006351:Heart Valves / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D006801:Humans; D008875:Middle Aged; D010496:Pericardium
D003094:Collagen