Abstract 624: Accumulation of Advanced Glycation End Products is Associated With Structural Degeneration of Bioprosthetic Heart Valves
Bibliographic record
Abstract
Introduction: Bioprosthetic heart valves (BHV) are widely used but frequently limited by structural valve degeneration (SVD), necessitating re-operation. Calcification is by far the best-studied SVD mechanism, but recent studies suggest that oxidative stress contributes to SVD. Advanced glycation end products (AGEs), formed by the ligation of sugar derivatives to proteins under oxidative conditions, mediate tissue degeneration in cardiovascular diseases. AGEs effect tissue damage through cross-linking and degradation of extracellular matrix proteins including collagen, a major structural component of BHV, as well as through exacerbation of inflammatory cell stimulation. Hypothesis: We hypothesize that AGEs accumulate in BHVs and are associated with oxidative stress-based SVD Methods: We performed immunohistochemistry for AGEs and specifically carboxymethyl lysine (CML) on sections of fixed, paraffin-embedded samples of degenerated bioprosthetic heart valves from 7 patients in the Penn Cardiac Bioregistry (4 male, 3 female, ages 40-83) and 4 short-term experimental Melody valve leaflets deployed in branch pulmonary arteries of 3 sheep. We correlated these results with levels of the circulating AGE receptor sRAGE via ELISA for patient BHV explants and with oxidized amino acid levels quantitated by mass spectrometry of di-tyrosine for experimental sheep BHV explants. Results: There was diffuse accumulation of AGEs in both clinical SVD and sheep explants of BHV. Immunohistochemistry reveals clear AGE and CML staining in all tested valves versus minimal to absent staining in unimplanted control samples. Staining intensity qualitatively correlated with overall di-tyrosine accumulation as well as sRAGE levels that were elevated in BHV patients. Notably, local staining for AGE in BHV is intensified in areas of calcification, thickening, and apparent inflammatory infiltration as well as in areas with structural damage. Conclusions: Extensive AGE accumulation was observed in both BHV explanted for SVD and sheep explants compared to controls, supporting the view that AGEs are associated with SVD pathophysiology. The association of AGE accumulation with di-tyrosine in BHV suggests that oxidative stress is a major mechanism of BHV SVD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".