Implication of Enhancer of Zeste Homolog 2 in Pulmonary Arterial Hypertension
Bibliographic record
Abstract
Background: Pulmonary arterial hypertension (PAH) is characterized by persistent elevation of pulmonary arterial (PA) pressure due to excessive proliferation and resistance to apoptosis of PA smooth muscle cells (PASMCs). Right ventricular (RV) failure is the cause of mortality associated with PAH, and is associated with maladaptive RV remodeling and fibrosis. Although epigenetic modifications are increasingly appreciated as an important contributing factor of PAH development, the precise mechanisms remain to be elucidated. EZH2 is a histone methyltransferase that is overexpressed in many cancers promoting cell proliferation and survival. Aim: Study the role of EZH2 in PAH progression. Methods and Results: Using Western blot (WB), we demonstrated that EZH2 is overexpressed in lungs, distal PAs and isolated PASMCs from PAH patients (p<0.01) as well as in the monocrotaline (MCT) and Sugen/Hypoxia rat models (p<0.05). Pharmacological or molecular inhibition of EZH2 leads to reduced PAH-PASMC proliferation (Ki67 labeling and EdU assay, p<0.001) and resistance to apoptosis (Annexin V assay p<0.001). These effects were accompanied by the expression changes of proteins associated with metabolism. In addition, we found that EZH2 is increased in human compensated RV but was decreased in PAH patients with decompensated RV failure (WB, p<0.05). Similar results were found in the MCT model in which the progression of RV remodeling was divided into 4 stages based on hemodynamic data. Conclusion: We demonstrated that EZH2 is implicated in PAH. Further research is required to understand precisely the role of EZH2 in lung and cardiac remodeling in the setting of PAH.
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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".