Abstract 18906: Congenital Right Ventricular Hypertrophy Compensation is Characterized by Sustained Angiogenesis
Bibliographic record
Abstract
The right ventricle (RV) is hypertrophied at birth and in the neonatal period. The RV regresses to a normal phenotype in the first month of life correlated with a concomitant drop PVR over that time. The RV may remain hypertrophied and compensated in response to maintained afterload in patients with congenital heart disease (CHD) for decades; whereas the hypertrophied RV acquired in adulthood from pulmonary arterial hypertension (PAH) quickly transitions to failure, and remains their primary determinant of mortality in PAH. Potentially, the transition from RV compensation to failure has been attributed to ischemia from deficient capillary density from inadequate angiogenesis in RV hypertrophy. Angiogenesis is largely regulated by the transcription factor hypoxia-inducible factor 1a (HIF1a), which governs the transcription of proangiogenic signaling effectors. Two such effectors strongly promoting angiogenesis under HIF1a regulation are vascular endothelial growth factor (VEGF) and stromal derived factor 1 (SDF1), which promote endothelial cell survival/proliferation and recruitment of CXCR4+ stem cells, respectively. We hypothesized that sustained HIF1a-driven angiogenesis maintains adequate RV vascularity in hypertrophy, thus preventing the transition from RV compensation to failure in CHD patients. The free walls of neonatal rat RVs had elevated levels of HIF1a (immunoblot and nuclear localization) compared to those of adult RVs, adult LVs, and neonatal LVs. This was associated with increased VEGF and SDF1 expression (Immunoblot and ELISA), which correlated with increased angiogenesis (matrigel assay) and CXCR4+ stem cell recruitment (Boyden chamber migration assay). Neonatal RVs had elevated expression vascular density (CD31 expression) and tissue perfusion (Lectin) compared to adult RVs, further supporting proangiogenic signaling. Human compensated RV hypertrophy myocardium from CHD patients had elevated SDF1 and CXCR4 expression compared to normal adult RV and LV myocardium (immunoblot), suggesting HIF1a driven angiogenic pathways are maintained in CHD tissues. Therapies that maintain HIF1a signaling may delay the transition from compensation to failure in adults with acquired 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) | 0.000 | 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) | 0.011 | 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".