Abstract 16814: A miRNA Signature of the Failing Right Ventricle
Bibliographic record
Abstract
INTRODUCTION: Right Ventricular Failure (RVF) is the most important prognostic structure for both morbidity and mortality in pulmonary hypertension (PHT) but remains understudied compared to the left ventricle (LV). Many differences (including embryologic origin) separate the 2 ventricles and the transition from a compensated to decompensated stage occurs much earlier in the RV vs the LV, in response to pressure overload. MicroRNAs (miRNAs) have emerged as important determinants of LV development and failure, but nothing is known about RV miRNAs. We hypothesized that specific miRNAs signatures may characterize the transition from the fetal to adult and from a compensated (CRV) to a decompensated (DRV) RV. METHODS/RESULTS: We studied free RV wall tissue from neonatal (Neo) and rats with normal RV function (NRV, RVSP=38±2 mmHg, CO=102±2 ml/min and RV/LV+Septum=22±1), CRV (RVSP=66±8 mmHg, CO=80±13 ml/min, RV/LV+Septum=48±3, 2-3 weeks post-monocrotaline) and DRV (RVSP=52±2 mmHg, CO=67±10 ml/min, RV/LV+Septum=58±2, ascites, weight loss, 4-6 weeks post monocrotaline) (n=6 in each group). We used Taqman Low Density Arrays to study the expression of 377 miRNAs. Neonates were separated clearly from other samples in both principal component analysis and hierarchical clustering analysis. 14 miRNAs were identified as differentially expressed between CRV, DRV and NRV (ANOVA applied on fold-change obtained after standard normalization procedures were performed (U6, median, quantile)). Among them, 7 showed a different pattern of expression compared to published data on LV hypertrophy: miR-200b, -132, -338-3p, -328, -155, -92a and -208. miR-208 has received attention as critical regulator of LVH. We showed that 208 decreased in CRV and DRV compared to NRV, whereas its expression is not known to decrease in LVH. This was confirmed by individual qRT-PCR and miR-208 levels were also found to negatively correlate with RV size (r=-0.72, n=20, p<0.001) as failure progresses. CONCLUSION: Further exploration of this unique miRNA signature, compared to LV, may also open new avenues of investigation on RVF. Since miR-208 is cardiac specific and regulated differently compared to LVH, it may offer important clues on why the RV responds suboptimally to pressure overload.
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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 | 0.001 |
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".