Loss of maternal atrial natriuretic peptide programs cardiac and renal gene expression: role of GATA4 and Npr‐1 in the fetal programming of cardiovascular health and disease
Bibliographic record
Abstract
Objective To determine the effect of loss of maternal atrial natriuretic peptide (ANP) on cardiac hypertrophy (CH) and salt‐sensitivity in offspring. Methods We obtained heterozygous offspring from ANP wild‐type (+/+) and knockout (−/−) dams (ANP+/− WT and ANP+/− KO offspring). Gene expression was measured using real‐time PCR. Results Maternal ANP had no effect on litter size or offspring growth. At 9‐weeks of age, ANP+/− KO had significantly higher left ventricular (LV) mass compared to ANP+/− WT . Left ventricular mRNA levels of ANP (a marker hypertrophy) and the pro‐hypertrophic factors GATA4 and P300 were significantly higher in ANP+/− KO mice. There was no significant difference in the hypertrophic response to daily injections of isoproterenol (ISO) between ANP+/− WT and ANP+/− KO , although CH remained significantly higher in ANP+/− KO . In the kidney of ANP+/− KO , we observed significantly higher mRNA levels of natriuretic peptide receptor 1 (Npr1), as well as P300 and Ets‐1, which are known to cooperatively stimulate Npr1 transcription. To determine the effect of elevated Npr1 on salt‐sensitivity, we treated offspring with a high salt diet for 5 weeks. Salt‐induced CH was only evident in ANP+/− WT and not ANP+/− KO mice. Conclusions Maternal ANP programs the structure and function of the cardio‐renal axis, and the loss of maternal ANP prevents salt‐sensitive CH in offspring, possibly via elevated renal Npr1. Grant Funding Source : Heart and Stroke Foundation of Ontario
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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) | 0.002 | 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".