Long Non-coding RNA H19 in Right Ventricular Failure associated with Pulmonary Arterial Hypertension
Bibliographic record
Abstract
Background: Right ventricular failure (RVF) is the major prognostic factor in pulmonary arterial hypertension (PAH). Recent Omics analyses have demonstrated the deregulation of several long non-coding RNAs (LncRNAs) in left heart failure, but their role in RVF remains unknown. The LncRNA H19 and its encoded miR-675 have been implicated in both cardiac hypertrophy and fibrosis (2 features of RVF) but never been studied in RVF. Methods and Results: By qRT-PCR, we showed in human RV biopsies obtained from control donors, compensated RV hypertrophy patients (CRVH, Cardiac index > 2.2) and decompensated RV hypertrophy patients (DRVH, PAH patients that died from RVF), that H19 and miR-675 were specifically up-regulated (p<0.001, n=10-12/group) in DRVH. Similar findings were found in the monocrotaline rat (MCT), a model characterized by PAH and DRVH. Interestingly H19/miR-675 up-regulation was RV specific as no change was seen in either the LV or lung of DRVH patients or in MCT. In 70 PAH patients, plasma levels of H19 were up-regulated (p<0.001) and correlated with PAH severity (pulmonary vascular resistance, cardiac index and pro-BNP) and prognosis. Mechanistically, we demonstrated that the up-regulation of H19/miR-675 is associated with reduced 4E-BP1, CaMKII-δ and Mitofusin 2, which were previously reported as H19 or miR-675 direct-targets and implicated in heart failure. Moreover, the down-regulation of H19 inhibited phenylephrine-induced cardiac hypertrophy in H9C2 cardiomyocytes. Conclusions: We demonstrated for the first time that H19 is implicated in the transition from CRVH to DRVH in human RVF. Circulating H19 represents a putative biomarker of RV function in PAH patients.
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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) | 0.001 | 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".