Abstract 443: The Role of Wnt5b and Wnt11 in Aortic Valve Calcification
Bibliographic record
Abstract
Introduction: The mechanisms underlying the pathogenesis of aortic valve calcification remain unclear. With accumulating evidence demonstrating that valve calcification recapitulates bone development, the crucial roles of non-canonical Wnt ligands Wnt5b and Wnt11 in osteogenesis make them critical targets in the study of aortic valve calcification. Hypothesis: We hypothesized that Wnt signaling mediated by ligands Wnt5b and Wnt11 is upregulated and the expression of these molecules may be associated with the pathological calcium deposition in aortic valves. Methods and Results: Mitral, non-calcified and calcified aortic valves were collected from patients with valve replacement. Total RNA was isolated, first strand cDNAs were synthesized and gene specific qPCRs were performed. The relative mRNA expression of Wnt5b and Wnt11 were calculated using the ΔΔCT method against GAPDH control and are expressed as fold change ± SEM compared to expression in non-calcified valves. We found significant increases in both Wnt5b (15.14±4.08) and Wnt11 (4.09±0.63) expression in calcified compared to non-calcified aortic or mitral valves (P<0.05). We also examined Wnt5b and Wnt11 protein expression in 73 mitral, non-calcified and calcified aortic valves by immunohistochemistry. There was little expression of Wnt11 or Wnt5b in normal aortic valves, normal segments of calcified valves or mitral valves. Wnt11 staining intensity was significantly elevated in areas of calcification, inflammation and in activated myointimal cells compared to normal aortic and mitral valves (P<0.05). Immunostaining for Wnt5b was expressed in similar cellular compartments as well as areas of fibrosis. Multivariant Spearman correlation analyses revealed significant positive correlations between Wnt5b and Wnt11 overall staining with calcification, lipid score, fibrosis, valve remodeling and microvessels (P<0.05). We are currently evaluating the tissue expression of these two molecules with clinical parameters of the disease. Conclusion: The upregulated Wnt5b and Wnt11 expression in calcified aortic valves, particularly in areas of calcification, fibrosis and activated myointimal cells suggests a potential involvement in the pathogenesis of aortic calcification.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".