Abstract 3770: Concentration-dependent Divergent Hypertrophic Effects of Estrogen in Adult Ventricular Myocytes
Bibliographic record
Abstract
High concentrations of estrogen have been shown to attenuate myocardial hypertrophy and left ventricular remodeling. However, the effects of low concentration of estrogen observed in postmenopausal women on cardiac hypertrophy have not been studied. In the present study we examined the effects of high (0.1 and 1 nM) and low (1 and 10 pM) concentration of the synthetic analog of estradiol, 17β-estradiol (E2) on adult cardiomyocytes (CMs). CMs were isolated from adult male and female Sprague-Dawley rats. The cells were used immediately after isolation to measure pH i or cultured to assess hypertrophic phenotype (cell surface area), gene markers (atrial natriuretic peptide, ANP), and protein activation. Low concentration of E2 (1 and 10 pM) increased cell surface area (females: 20%, P <0.05; males: 28%, P <0.05) and ANP expression (females: 394%, P <0.05; males: 497%, P <0.05) after 24 h. However, high concentrations (0.1 and 1 nM) of E2 did not induce cell hypertrophy but instead blocked the hypertrophic effect of the α 1 -agonist phenylephrinerophy. The pro-hypertrophic effect of low concentration of E2 was prevented by the sodium-hydrogen exchange isoform 1 (NHE-1) specific inhibitor AVE-4890 (AVE, 5 μM) suggesting involvement of NHE-1 in mediating the E2-induced hypertrophy. Fluorometric measurements with the pH i -sensitive dye BCECF demonstrated that a 1 pM E2 increased the pH i (females: +0.05 pH units; males +0.12 pH units, P <0.05) by a rapid non-genomic mechanism that was blocked by AVE. On the other hand, 1 nM E2 decreased the pH i (females: −0.24 pH units, P <0.05; males: −0.07 pH units, P <0.05) and this effect was also prevented by AVE. The NHE-1-mediated pro-hypertrophic effect of 1 pM E2 was dependent on phosphorylation of ERK1/2 MAPK since the effect was blocked with the ERK1/2 inhibitor PD98059 (10 μM) and there was no gender difference on ERK1/2 activation. E2 has a dual concentration-dependent role in adult CMs as manifested by a pro-hypertrophic effect at low concentrations (1 and 10 pM), and conversely, an anti-hypertrophic effect at high concentrations (0.1 and 1 nM). The pro-hypertrophic effect of E2 is mediated, at least in part, through ERK1/2/NHE-1 activation.
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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) | 0.003 | 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".