Long noncoding RNA H19 in the pathogenesis of right ventricular failure with pulmonary arterial hypertension
Bibliographic record
Abstract
Background: Right ventricular (RV) failure is an important prognostic factor for pulmonary arterial hypertension (PAH). RV failure in PAH is associated with increased ischemia and decreased RV wall perfusion due to repressing angiogenesis and remodeled coronary circulation. The mechanism of RV failure remains poorly understood. Recently the role of H19, a long noncoding RNA highly expressed in the heart, has been investigated in left ventricular failure. Its role in RV remains unknown. Methods and Results: Using Taq-Man qRT-PCR, we demonstrated that H19 and its mature product miR-675 were up-regulated in RVs (but not in the LVs) from PAH patients compared to those from controls (n=8 each). In addition, H19 was negatively correlated with cardiac index. Interestingly H19 expression was not changed in lung of PAH patients compare to control. Similar findings were obtained in the PAH monocrotaline rat model. From a mechanistic point of view we showed that H19 upregulation in PAH RV was associated with repression of its targets calcium/calmodulin-dependent protein kinase II δ (a critical regulator of MEF2 signaling which is implicated in heart failure) and AKT signaling (a major regulator of NFAT signaling implicated in cardiac hypertrophy and angiogenesis) in the RVs from PAH patients (western blot, n=8-9, all p<0.05). Conclusions: We demonstrated for the first time that H19 upregulation is associated with RV failure due to PAH, which could potentially lead to RV-specific novel biomarkers and therapeutic targets.
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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".