06 Epoxyeicosatrienoic acid mediated cardioprotection involves mitochondrial caveolin-1 and PKCe
Bibliographic record
Abstract
Cytochrome P450 epoxygenases can metabolise arachidonic acid to epoxyeicosatrienoic acids (EETs) which have known cardioprotective effects. Subsequent metabolism of EETs by soluble epoxide hydrolase (sEH) reduces the protective effect. Caveolins (Cav-1, -2, and -3) are structural proteins that insert into the plasma membrane to form caveolae, which bind molecules important in cardiac signal transduction and function. The objective of this study was to assess the role of caveolins and PKCε in EET mediated cardioprotection. Hearts from sEH null (KO) and littermate control (WT) mice were perfused in Langendorff mode and subjected to 20 min ischaemia followed by 40 min reperfusion. Immunohistochemistry, immunoblot and electron microscopy were performed to study expression and ultrastructure. H9c2 cells were treated with 11,12-EET (1 μM) for 10, 20, 60 and 120 min followed by subcellular fractionation and immunobloting. In WT heart, cav-1 and cav-3 were present in cardiomyocytes and endothelial cells at baseline. Following ischaemia, cav-1 but not cav-3 disappeared; moreover, caveolae were absent in WT hearts. Mitochondria and T-tubules were swollen and cristae of mitochondria were damaged. Improved post-ischaemic functional recovery observed in KO or WT hearts treated with 11,12-EET corresponded with higher cav-1 expression in plasma membrane and mitochondrial fractions. Increased phosphoPKCε expression was observed in mitochondrial fractions of 11,12-EET treated hearts. H9c2 cells treated with 11,12-EETs showed a time-dependent increased in cav-1 and phosphoPKCε expression in mitochondrial fractions. Taken together, our data suggest EET-mediated cardioprotection results in increased mitochondrial expression of cav-1 and phosphoPKCɛ.
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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 | 0.000 | 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) | 0.000 | 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".