Inhibition of the receptor of advanced glycation reverses pulmonary arterial hypertension
Bibliographic record
Abstract
Pulmonary arterial (PA) hypertension (PAH) is a vasculopathy characterized by enhanced PA smooth muscle cells (PASMC) proliferation and suppressed apoptosis. A recent proteomic analysis of PAH lungs demonstrated that the receptor of advanced glycation endproducts (RAGE) is one of the most upregulated proteins in PAH patients. We hypothesized that RAGE could play a critical role in PAH etiology and progression. We demonstrated a specific RAGE overexpression in PAH lungs. In human PASMC, we showed that RAGE was implicated in the proliferative and apoptosis‐resistant phenotype. Recent studies demonstrated an altered BMPR2 (Bone Morphogenetic Protein Receptor 2)/PPARγ (Peroxisome Proliferator‐Activated Receptor gamma) axis in PAH. We showed that RAGE is accountable for BMPR2/PPARγ downregulation, thus regulating proliferation and apoptosis. In vivo , RAGE inhibition (siRNA nebulization) in rats with Sugen‐induced PAH showed decreased PA pressure and right ventricular hypertrophy, associated with a significant improvement in lung perfusion and decreased PA wall thickness. To conclude, w e demonstrated the implication of RAGE in PAH etiology. Thus, RAGE inhibitors, which are in clinical phase II for Alzheimer's disease, represent potential therapeutic agents for PAH treatment. A Canadian Thoracic Society scholarship to JM and Canadian Institutes of Health Research grants to SB supported this work.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".