Cardiac xenotransplantation technology provides materials for improved bioprosthetic heart valves.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY.
(pp. 269 - 275).
Objectives: Human subjects and Old World primates have high levels of antibody to galactose-alpha-1,3 galactose beta-1,4-N-acetylglucosamine (alpha-Gal). Commercially available bioprosthetic heart valves of porcine and bovine origin retain the Gal antigen despite current processing techniques. Gal-deficient pigs eliminate this xenoantigen. This study tests whether binding of human anti-Gal antibody effects calcification of wild-type and Gal-deficient glutaraldehyde-fixed porcine pericardium by using a standard subcutaneous implant model.Methods: Expression of alpha-Gal was characterized by lectin Griffonia simplicifolia-IB4 staining. Glutaraldehyde-fixed pericardial disks from Gal-positive and Gal-deficient pigs were implanted into 12-day-old Wistar rats and 1.5-kg rabbits with and without prelabeling with affinity-purified human anti-Gal antibody. Calcification of the implants was determined after 3 weeks by using inductively coupled plasma spectroscopy.Results: The alpha-Gal antigen was detected in wild-type but not Gal-deficient porcine pericardium. Wild-type disks prelabeled with human anti-Gal antibody exhibited significantly greater calcification compared with that seen in antibody-free wild-type samples (mean +/- standard error of the mean: 111 +/- 8.4 and 74 +/- 9.6 mg/g, respectively; P = .01). In the presence of anti-Gal antibody, a significantly greater level of calcification was detected in wild-type compared with GTKO porcine pericardium (111 +/- 8.4 and 55 +/- 11.8 mg/g, respectively; P = .005). Calcification of Gal-deficient pericardium was not affected by the presence of anti-Gal antibody (51 +/- 9.1 and 55 +/- 11.8 mg/g).Conclusions: In this model anti-Gal antibody accelerates calcification of wild-type but not Gal-deficient glutaraldehyde- fixed pericardium. This study suggests that preformed anti-Gal antibody present in all patientsmight contribute to calcification of currently used bioprosthetic heart valves. Gal-deficient pigsmight become the preferred source for new, potentially calcium-resistant bioprosthetic heart valves. (J Thorac Cardiovasc Surg 2011;141:269-75)
|Title:||Cardiac xenotransplantation technology provides materials for improved bioprosthetic heart valves|
|Event:||90th Annual Meeting of the American-Association-for-Thoracic-Surgery|
|Dates:||2010-05-01 - 2010-05-05|
|Keywords:||GAL ANTIBODY, VALVULAR BIOPROSTHESES, IMMUNE-RESPONSE, KNOCKOUT PIGS, ALPHA-GAL, CALCIFICATION, REJECTION, BABOONS, CELLS, GENE|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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