Abstract 16778: Cardiac Hypertrophy in Neonates With Congenital Heart Disease Delays Maturational Changes in Cardiac Energy Metabolism via Decreased Mitochondrial Acetylation
Bibliographic record
Abstract
Background: A rapid increase in fatty acid oxidation occurs in the heart following birth. However, cardiac hypertrophy, that occurs secondary to congenital heart diseases (CHDs), delays this normal maturation of fatty acid oxidation, thereby decreasing energetic capacity and increasing the susceptibility of the heart to ischemic injury during corrective surgery. Recently, increased cardiac acetylation has emerged as an important post-translational modification that increases fatty acid oxidation. We therefore examined what effect cardiac hypertrophy has on the acetylation control of fatty acid oxidation in the human neonates. Methods and Results: A total of 145 right ventricular biopsy samples were collected from neonatal patients undergoing corrective surgery for CHDs, and were stratified according to patient age (0-20 days, n=58; 21-100 days, n=41; and 101-200 days, n=46), as well as the absence (n=83) or presence (n=62) of hypertrophy (assessed by echocardiography). An increase in overall myocardial protein acetylation was seen with increasing age in non-hypertrophied hearts. In contrast, no age-dependent increase in acetylation was observed in hypertrophied hearts, in concert with an increase in mitochondrial deacetylase SIRT3, and a blunted increase in mitochondrial acetyltransferase GCN5L1. An age-dependent hyperacetylation of the fatty acid oxidation enzymes long chain acyl CoA dehydrogenase (LCAD) and β-hydroxyacyl CoA dehydrogenase (β-HAD) was observed only in non-hypertrophied hearts, which was positively correlated with their enzyme activities. Similar results were also observed in a volume-overload hypertrophy in newborn rabbits, where decreased acetylation of LCAD and β-HAD and decreased fatty acid oxidation was evident compared to non-hypertrophied rabbit hearts. Furthermore, acetylation of PGC-1α, a transcriptional regulator for mitochondrial biogenesis, decreased with age only in non-hypertrophied hearts, along with decreased expression of the nuclear acetyltransferase GCN5 and nuclear deacetylase SIRT6. Conclusions: The presence of cardiac hypertrophy in CHDs patients prevents the normal increase in myocardial acetylation following birth, resulting in a delayed maturation of fatty acid oxidation.
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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 | 0.001 |
| 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) | 0.004 | 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".