Gal knockout pig pericardium: new source of material for heart valve bioprostheses.
BACKGROUND
Although glutaraldehyde fixation is known to reduce immunogenicity and degeneration of heart valve bioprostheses, some degree of immunogenicity persists, which may trigger calcification. The aims of this study were to: (1) define the role of alpha-1,3-galactosyltransferase (alpha-Gal) antigen in valve calcification by comparing alpha-Gal-positive and alpha-Gal-deficient (GT-KO) pig pericardium; and (2) elucidate the role of human anti-Gal antibodies in the process of calcification and to determine the potential influence of different tissue-fixation techniques.


METHODS
Glutaraldehyde-treated pericardium from alpha-Gal-positive and GT-KO pigs, with or without pre-labeling with human anti-Gal antibodies, were implanted in rats during 1 month.


RESULTS
In glutaraldehyde-fixed pericardium, calcification levels were significantly lower in GT-KO pig pericardium (132.8 +/- 5.8 microg/mg) as compared with alpha-Gal-positive pig pericardium (155.7 +/- 7.1 microg/mg) (p < 0.015). In glutaraldehyde-fixed pig pericardium followed by a mix of formaldehyde, ethanol and Tween 80 (FET), the calcification levels were lower in GT-KO pig pericardium (0.35 +/- 0.1 microg/mg) as compared with alpha-Gal-positive pig pericardium (4.6 +/- 4.2 microg/mg). In glutaraldehyde-fixed pig pericardium + FET pre-incubated with human anti-Gal antibodies, calcification levels were significantly greater in alpha-Gal-positive pig pericardium (43.8 +/- 8.5 microg/mg) as compared with GT-KO pig pericardium (5.7 +/- 2.9 microg/mg) (p < 0.0001).


CONCLUSIONS
This study demonstrates the role of alpha-Gal antigen and human alpha-Gal antibodies in the calcification process of valvular bioprostheses. It is suggested that GT-KO pig pericardium could be beneficial as a new source of material for heart valve bioprostheses.
Lila
Nermine
N
Laboratory of Biosurgical Researches, University Paris Descartes, Georges Pompidou Hospital, Paris, France. nerminelila@yahoo.fr
McGregor
Christopher G A
CG
Carpentier
Sophie
S
Rancic
Jeanne
J
Byrne
Guerard W
GW
Carpentier
Alain
A
D000818:Animals; D030801:Animals, Genetically Modified; D000910:Antibodies, Heterophile / Q000032:analysis; D001705:Bioprosthesis; D002114:Calcinosis / Q000276:immunology / Q000473:pathology; D019544:Equipment Failure Analysis; D005700:Galactosyltransferases / Q000235:genetics*; D055786:Gene Knockout Techniques; D006350:Heart Valve Prosthesis; D006801:Humans; D008856:Microscopy, Fluorescence; D010496:Pericardium / Q000276:immunology* / Q000473:pathology; D013552:Swine / Q000235:genetics*; D016707:Tissue Fixation; D014183:Transplantation, Heterologous
D000910:Antibodies, Heterophile; D005700:Galactosyltransferases; C530267:alpha-1,3-galactosyltransferase 1, porcine