The Role of DNMT and HDACs in the Fetal Programming of Hypertension by Glucocorticoids
Bibliographic record
Abstract
The causes of hypertension are complex and involve both genetic and environmental factors. Environment changes during fetal development have been linked to adult diseases including hypertension. Studies show that timed in utero exposure to the synthetic glucocorticoid (GC) dexamethasone (Dex) results in the development of hypertension in adult rats. Evidence suggests that in utero stress can alter patterns of gene expression, possibly a result of alterations in the topology of the genome by epigenetic markers such as DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). The objective of this study was to determine the effects of epigenetic regulators in the fetal programming and the development of adult hypertension. Specifically, this research examined the effects of the HDAC inhibitor valproic acid (VPA) and the DNMT inhibitor 5-aza-2<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:msup><mml:mrow/><mml:mrow><mml:mo>′</mml:mo></mml:mrow></mml:msup></mml:math>-deoxycytidine (5aza2DC) on blood pressure (BP) and gene expression in prenatal Dex-programmed rats. Data suggest that both VPA and 5aza2DC attenuated the Dex-mediated development of hypertension and restored BP to control levels. Epigenetic DNMT inhibition (DNMTi) or HDAC inhibition (HDACi) also successfully attenuated elevations in the majority of altered catecholamine (CA) enzyme expression, phenylethanolamine N -methyltransferase (PNMT) protein, and elevated epinephrine (Epi) levels in males. Although females responded to HDACi similar to males, DNMTi drove increased glucocorticoid receptor (GR) and PNMT expression and elevations in circulating Epi in females despite showing normotensive BP.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".