P117 <break /> Macitentan prevents pulmonary fibrosis progression and secondary pulmonary hypertension induced by TGF-β1 overexpression in rats
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Bibliographic record
Abstract
Idiopathic pulmonary fibrosis is a progressive disease with unknown cause and limited treatment options. Pulmonary hypertension (PH) is frequent in patients and is a prognostic marker indicating increased mortality risk. We already demonstrated that PH develops in a rat model of overexpression of Transforming-Growth-Factor-β1 (AdTGF-β1). Macitentan (Opsumit®) is an endothelin receptor antagonist which is approved for treatment of pulmonary arterial hypertension, a life-threatening disorder which compromises lungs’ and heart’s function. We hypothesized that Macitentan will improve PH and fibrosis progression induced by AdTGF-β1. Rats received AdTGF-β1 (D0) and daily gavage of macitentan, pirfenidone, their combination or saline (D14-D28). Pulmonary artery pressure (PAP) was measured using a pressure catheter (SPR-407). Fibrosis was evaluated by morphometric measurements coupled with hydroxyproline assay. AdTGF-β1 induced lung fibrosis with an increase in collagen deposition combined with a significant increase in PAP compared to controls. Treatment with pirfenidone prevented fibrosis progression as shown by a reduction in collagen deposition and a decrease in fibrotic areas of the lung at D28. However, pirfenidone treatment did not affect the PAP increase induced by AdTGF-β1. Treatment with macitentan prevented the increase in PAP induced by AdTGF-β1 and also prevented fibrosis progression from D14 to D28 as shown by a reduction in collagen deposition and a decrease in fibrotic areas of the lung. The combination of both drugs prevented PAP increase and fibrosis progression.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it