Abstract 18802: Transcriptome Profiles of Chronically Closed or Cycling Aortic Valve Leaflets are Highly Similar Compared to Chronically Open Valves: Distention Drives Leaflet Homeostasis
Bibliographic record
Abstract
Introduction: Throughout the valve cycle mechanical forces of multiple types and intensities are exerted on the leaflets, sinus and annulus. The mechanisms through which these forces regulate the homeostatic maintenance of valve leaflet architecture are still poorly understood. Ventricular mechanical support with a continuous flow device results in chronic closure of the outflow valve. Whether chronic valve closure affects valve leaflet homeostasis is a significant but unsettled clinical concern. Hypothesis: We asked if chronic closure of the aortic valve (AV) impairs leaflet homeostasis by comparing the transcriptome profiles of AV cultured under different mechanical force conditions: Normally cycling (Flow); Not cycling but open (Static); or Not cycling but closed (Static-Closed, SC). Methods: Ex vivo culture of native rat aortic valves, (8 valves per bioreactor, 4 valves per condition) was conducted in a flow bioreactor for seven days at 37C in endothelial cell culture media under conditions approximating the normal stroke volume of the rat heart. In each of 4 independent experiments, flow-induced valve cycling (Flow) was compared with either Static or SC condition in paired groups. After culture, leaflets were dissected from 3 valves/condition and pooled, mRNA was extracted and expression was evaluated using whole genome microarrays. Results: Statistical-based unsupervised hierarchical clustering analysis of the leaflet transcriptome profiles revealed only two distinct patterns of leaflet gene expression between the three groups of AV. Flow and SC groups had nearly identical profiles whereas the Static valve group was distinctly different (p<0.05). Conclusions: These results reveal that the stretching of valve leaflets by a filling volume inducing full coaptation is apparently sufficient to largely preserve their architecture and phenotypic gene expression in the seven day culture period tested. In contrast, the absence of valve closure produces a markedly different pattern of gene expression. Therefore, the absence of flow through the closed AV valve does not appear to be inherently destructive compared with conditions in which the valve remains open.
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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) | 0.002 | 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".