Abstract 16942: Effects of BMPR2 Mutations on Global MicroRNA Expression Profiles in Blood Outgrowth Endothelial Cells from Patients with Pulmonary Arterial Hypertension
Bibliographic record
Abstract
Background: Mutations of the bone morphogenetic protein receptor 2 gene ( BMPR2 ) are found in patients with heritable (H) or idiopathic (I) pulmonary arterial hypertension (PAH). However, their role in abnormalities of endothelial cell (EC) growth and survival in PAH is unclear. Therefore, blood-outgrowth endothelial cells (BOECs), which closely resemble mature endothelial cells, were used to study patient-specific effects of BMPR2 mutations on endothelial microRNAs (miRNA), which are recognized to be key regulators of gene expression. Hypothesis: Disease-specific alterations in miRNA expression profiles in BOECs from patients with HPAH or IPAH, with and without BMPR2 mutations, contribute to the previously reported abnormalities in EC growth and survival in this disease. Methods: BOECs were derived from the peripheral blood mononuclear cell fraction isolated from 7 patients (4 HPAH with BMPR2 mutations, and 3 IPAH) and 5 healthy controls (including 1 unaffected BMPR2 mutation carrier). Cells were characterized by cobblestone morphology and surface marker profile (cd31+/cd45-/cd14-/cd34+/KDR+). 1066 miRNAs were measured using an (RT)-qPCR array platform (Qiagen), and normalized with a mean-centering restricted method. Results: 767 ± 30 miRNAs were detected in BOECs from the 12 participants (PCR Cq cutoff BMPR2 mutations vs. controls (p BMPR2 mutation carrier. Conclusion: A global analysis of miRNAs in BOECs revealed distinct profiles in IPAH and HPAH patients, with both disease- and BMPR2 mutation-specific patterns of expression. These data suggest that unique miRNAs may contribute to alterations in endothelial gene expression that underlie abnormalities in EC growth and survival, and may be novel targets for therapeutic and biomarker development.
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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) | 0.002 | 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".