Changes in the Left Ventricular Eicosanoid Profile in Human Dilated Cardiomyopathy
Bibliographic record
Abstract
Objective: -6 polyunsaturated fatty acids (PUFAs) have both beneficial and detrimental effects on the heart. However, contribution of these lipid mediators to dilated cardiomyopathy (DCM)-associated mitochondrial dysfunction remains unknown. This study aimed to characterize DCM-specific alterations in the PUFA metabolome in conjunction with cardiac mitochondrial quality in human explanted heart tissues. Methods: -6 PUFA metabolism were quantified. Cardiac mitochondrial quality was assessed by transmission electron microscopy, measurement of respiratory chain complex activities and oxygen consumption (respiratory control ratio, RCR) during ADP-stimulated ATP production. Results: Formation of cardioprotective CYP-derived lipid mediators, epoxy fatty acids (EpFAs), and their corresponding diols were enhanced in DCM hearts. These findings were corroborated by increased expression of CYP2J2 and CYP2C8 enzymes, as well as microsomal and soluble epoxide hydrolase enzymes, suggesting enhanced metabolic flux and EpFA substrate turnover. DCM hearts demonstrated marked damage to mitochondrial ultrastructure and attenuated mitochondrial function. Incubation of fresh DCM cardiac fibers with the protective EpFA, 19,20-EDP, significantly improved mitochondrial function. Conclusions: The current study demonstrates that increased expressions of CYP-epoxygenase enzymes and epoxide hydrolases in the DCM heart correspond with enhanced PUFA-derived EpFA turnover. This is accompanied by severe mitochondrial functional impairment which can be rescued by the administration of exogenous EpFAs.
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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) | 0.001 | 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".