miR-126; link between angiogenesis and exercise intolerance in pulmonary arterial hypertension
Bibliographic record
Abstract
INTRODUCTION: Pulmonary arterial hypertension (PAH) is characterized by a significant exercise intolerance which does not correlates with the cardiac output at rest and during exercise. Thus intrinsic skeletal muscle dysfunctions may contribute to exercise intolerance in PAH. Several studies have shown a close relationship between muscle circulation, exercise capacity and miR-126, an endothelial specific pro-angiogenic miRNA. We hypothesized that miR-126 is downregulated in peripheral muscles of PAH patients, decreasing microcirculation and contributing to exercise intolerance. METHODS/RESULTS: Compared to control patients matched by both age and sex, PAH patients displayed dramatic decrease in exercise tolerance. This decrease correlates with a significant diminution in quadriceps microcirculation measured by CD31 immunofluorescence. At the cellular level, the decrease in microcirculation was associated with a significant downregulation of miR-126 expression Interestingly microcirculation and miR-126 expression are also decreased in intercostal muscle of PAH patient compared to control. In vitro, using freshly isolated CD31+ cells from human quadriceps biopsies; we demonstrated that the downregulation of miR-126 triggered the activation of SPRED-1 leading to VEGF/ERK pathway effector downregulation in PAH impairing the angiogenic response. All these abnormalities were reversed by treating the cells with miR126 mimic; while inhibition of miR126 in healthy CD31+ cells fully mimic the PAH phenotype. CONCLUSION: We demonstrated for the first time that exercise intolerance in PAH is associated with the decrease of skeletal muscle angiogenesis secondary to the downregulation of miR-126.
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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) | 0.001 | 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".