Abstract 4146495: Branched Chain Amino Acids Modulate Lung-Liver Axis in Pulmonary Arterial Hypertension
Bibliographic record
Abstract
Background: Valine, leucine, and isoleucine are the branched amino acids (BCAA). Elevated BCAAs predict worse outcomes in several cardiovascular diseases with metabolic origins, but the role of BCAAs in pulmonary arterial hypertension (PAH) remains unclear. Moreover, the effects of BCAAs on the emerging lung-liver axis are unexplored. Methods: The effects of small molecule (BT2) activation of BCAA catabolism and a low BCAA diet were evaluated in monocrotaline rats. Multi-omics analyses of the lung and liver were conducted in the BT2 arm. Confocal microscopy evaluated hepatocyte nuclear size in rodents and humans with PAH. Human livers were subjected to proteomic analysis. Human single nucleotide polymorphisms (SNPs) associated with elevated BCAAs and their relationship with PAH were investigated in the BioVU database. Results: Proteomics and metabolomics profiling demonstrated BT2 restructured lung fat metabolism, which increased exercise capacity, reduced PAH severity, and improved RV function. A low BCAA diet also mitigated PAH severity and improved RV function. Pathological hepatic shear stress phenotypes induced by RV dysfunction (nuclear hypertrophy, AKT signaling, electron transport chain (ETC) homeostasis, and ceramide accumulation) were blunted by BT2. Human PAH livers partially phenocopied the rodent hepatic shear stress phenotype (nuclear enlargement, AKT activation, and ETC protein downregulation). Finally, patients harboring SNP rs117643180 had increased risk of PAH. Conclusion: Rodent and human data link altered BCAA catabolism to the pathogenic lung-liver axis in 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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.014 | 0.002 |
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".