Quantification of Alpha-Gal Expression in Commercial BioProsthetic Heart Valves and Its Potential Mitigation

Area of Science:

• Biomaterials Science
• Immunology
• Cardiovascular Research

Background:

• Bioprosthetic heart valves (BHVs) degenerate due to mechanical stress, lipid infiltration, and calcification.
• The αGal antigen (galactose-α-1,3-galactose) contributes to BHV deterioration by activating innate immune pathways.
• Understanding xenoantigen presence and degradation is crucial for improving BHV longevity.

Purpose of the Study:

• Quantify residual αGal xenoantigens in commercial BHVs.
• Evaluate a polyphenol treatment for neutralizing αGal antigens.
• Investigate long-term glutaraldehyde fixation stability and αGal re-exposure.

Main Methods:

• Analyzed 12 BHV models for αGal quantification before and after polyphenol treatment.
• Simulated long-term BHV material behavior by incubating glutaraldehyde-fixed tissues for up to 9 years.
• Assessed antigen unmasking due to glutaraldehyde degradation.

Main Results:

• BHVs showed significant αGal epitope presence (4.18-8.51 × 10^11/10 mg).
• Polyphenol treatment reduced detectable αGal epitopes by approximately 99%.
• Prolonged incubation led to up to 60% re-exposure of αGal antigens due to glutaraldehyde degradation.

Conclusions:

• Commercial BHVs retain immunogenic αGal xenoantigens.
• Glutaraldehyde crosslink degradation over time re-exposes αGal epitopes, potentially affecting valve performance.
• Polyphenol treatment shows promise for enhancing BHV biocompatibility by inhibiting αGal antigens.