2‐Methoxyestradiol protect against cardiac hypertrophy induced by abdominal aortic constriction
Bibliographic record
Abstract
Numerous experimental studies have supported the evidence that 2‐methoxyestradiol (2ME) is a biologically active metabolite and mediates multiple effects on the cardiovascular systems that are largely independent of estrogen receptor. 2ME is a major cytochrome P450 1B1 (CYP1B1) metabolite and has been reported to have a vasoprotective and anti‐inflammatory actions. However, whether 2ME would prevent cardiac hypertrophy induced by abdominal aortic constriction (AAC) has not been investigated yet. Therefore, the overall objectives of the present study are to elucidate the potential anti‐hypertrophic effect of 2ME and to explore the mechanism(s) involved. For this purpose, Sprague–Dawley rats were subjected to either sham or abdominal aortic constriction surgery to induce cardiac hypertrophy and treated with 2ME or vehicle. Thereafter, cardiac hypertrophy parameters were determined using echocardiography whereas, protein expression level and the formation of mid‐chain hydroxyeicosatetraenoic acid (mid‐chain HETEs) were measured using western blot analysis and liquid chromatography‐electron spray ionization‐mass spectrometry, respectively. Our results showed that 2ME significantly inhibited cardiac hypertrophy induced by AAC as evidenced by a decrease in the heart weight to tibial length ratio and left ventricular morphology such as intraventricular septum, left ventricular internal diameter and left ventricular posterior wall. Mechanistically, the protective effect of 2ME against cardiac hypertrophy induced by AAC was mediated through a significant inhibition of CYP1B1 and its associated cardiotoxic metabolites mid‐chain HETEs. Our study provides the first evidence that 2ME prevents cardiac hypertrophy induced by AAC through CYP1B1 and mid‐chain HETEs‐dependent mechanisms. Support or Funding Information This work was supported by a grant from the CIHR to A.O.S.E. Z.H.M. is the recipient Izaak Walton Killam and Alberta Innovates‐Health solution Scholarships.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.001 | 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".