Celastrol has beneficial effects on pulmonary hypertension associated with bronchopulmonary dysplasia: Preclinical study outcomes
Bibliographic record
Abstract
Pulmonary hypertension associated with bronchopulmonary dysplasia (BPD-PH) is a severe cardiorespiratory disease of preterm newborns leading to an excess of mortality in infancy and no curative treatment currently exists. Inflammation and oxidative stress are the common pathways that lead to BPD-PH. Therefore, we aimed to evaluate celastrol, a molecule with anti-inflammatory and antioxidant properties, as a promising preventive treatment in BPD-PH. In a model of neonatal rats exposed to hyperoxia, we demonstrated that mortality was prevented in animals treated with celastrol. Moreover, in vivo , celastrol decreased pulmonary hypertension, right ventricular hypertrophy, vascular remodeling, pulmonary arterial hyperreactivity to endothelin-1 and inflammation but had no effect on hypoalveolarization and altered angiogenesis. In vitro experiments carried out on human fetal pulmonary artery smooth muscle cells (HfPA-SMC) exposed to hyperoxia showed that endothelin-1-induced intracellular calcium response was increased and celastrol significantly inhibited this effect, without modifying endothelin-1 receptors expression. Regarding inflammation, celastrol decreased both CD68 staining in lung and secretion of the pro-inflammatory cytokine Tissue Inhibitor of Metalloproteinases-1 in intrapulmonary arteries from neonatal rats. IL-6 secretion was also decreased by celastrol in HfPA-SMC. Finally, hyperoxia increased heme oxygenase-1 (HO-1) expression and celastrol induced an overexpression of HO-1 in both neonatal rat lung and human cells. These results suggest that celastrol has a preventive effect on major hallmarks of PH in both a rat hyperoxic model of BPD-PH and HfPA-SMC exposed to hyperoxia via modulation of macrophage inflammatory signaling and HfPA-SMC calcium cycling. Celastrol could therefore be considered as a promising preventive treatment in BPD-PH. • BPD-PH is a severe disease increasing mortality within 2 years after diagnosis. • Celastrol decreases main hallmarks of PH in both animal and human models. • Celastrol benefits prevent mortality in a neonatal rat model of BPD-PH. • Celastrol is a promising preventive therapeutic option for BPD-PH. • We developed HfPA-SMC exposed to hyperoxia as a new in vitro model of prematurity.
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How this classification was reachedexpand
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".