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 (α-Gal) antigen in valve calcification by comparing α-Gal–positive and α-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 α-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 μg/mg) as compared with α-Gal–positive pig pericardium (155.7 ± 7.1 μg/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 μg/mg) as compared with α-Gal–positive pig pericardium (4.6 ± 4.2 μg/mg). In glutaraldehyde-fixed pig pericardium + FET pre-incubated with human anti-Gal antibodies, calcification levels were significantly greater in α-Gal–positive pig pericardium (43.8 ± 8.5 μg/mg) as compared with GT-KO pig pericardium (5.7 ± 2.9 μg/mg) (p < 0.0001).

Conclusions

This study demonstrates the role of α-Gal antigen and human α-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.

Keywords: heart valve bioprostheses, immunogenicity, calcification, alpha-gal, anti-gal antibodies