Resveratrol Protects Against Angiotensin II‐Induced Cellular Hypertrophy through Inhibition of CYP1B1/Mid‐Chain Hydroxyeicosatetraenoic Acid Mechanism
Bibliographic record
Abstract
Objective Cytochrome P450 1B1 (CYP1B1) and its associated cardiotoxic mid‐chain hydroxyeicosatetraenoic acid (HETEs) metabolites have been reported to directly contribute to the development of cardiac hypertrophy. Resveratrol (RESV) is naturally occurring and commercially available polyphenol that possess beneficial effects in wide array of cardiovascular diseases. Several reports have shown the capacity of RESV to treat cardiac hypertrophy, myocardial infarction and heart failure. However, the underlying mechanisms, responsible for RESV beneficial effects, are not fully elucidated. Since RESV is a well‐known CYP1B1 inhibitor, the purpose of this study is to investigate whether RESV protects against angiotensin II (Ang II)‐induced cellular hypertrophy through inhibition of CYP1B1/mid‐chain HETEs mechanism. Methods Human ventricular cardiomyocytes RL‐14 and rat cardiomyoblast H9c2 cells were treated with vehicle or 10 μM Ang II in the absence and presence of 2, 10 or 50 μM RESV for 24 h. Thereafter, the level of mid‐chain HETEs was determined using liquid chromatography–mass spectrometry (LC/MS). Hypertrophic markers and CYP gene expression and protein levels were measured using real‐time PCR and Western blot analysis, respectively. Results Our results demonstrated that RESV, at concentrations of 10 and 50 μM, was able to protect against Ang‐II‐induced cellular hypertrophy as evidenced by a substantial inhibition of hypertrophic markers, β‐myosin heavy chain (MHC)/α‐MHC and atrial natriuretic peptide (ANP). Ang II significantly induced the protein expression of CYP1B1 and increased the metabolite formation rate of its associated mid‐chain HETEs namely 5‐, 8‐, 9‐, 12‐ and 15‐HETE in both cell lines. Interestingly, the protective effect of RESV, at concentrations 10 and 50 μM, was associated with a significant decrease of CYP1B1 protein expression and mid‐chain HETEs to nearly control levels. Conclusion Our results provided the first evidence that RESV protects against Ang II‐induced cellular hypertrophy, at least in part, through CYP1B1/mid‐chain HETEs‐dependent mechanism. Support or Funding Information This work was supported by a grant from the Canadian Institutes of Health Research [Grant 106665] to A.O.S.E. S.M.S. is the recipient of Antoine Noujaim Graduate Scholarship in Pharmaceutical Sciences. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| 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".