Chronic activation of PPARα is detrimental to cardiac recovery after ischemia
Bibliographic record
Abstract
High fatty acid oxidation (FAO) rates contribute to ischemia-reperfusion injury of the myocardium. Because peroxisome proliferator-activated receptor (PPAR)alpha regulates transcription of several FAO enzymes in the heart, we examined the response of mice with cardiac-restricted overexpression of PPARalpha (MHC-PPARalpha) or whole body PPARalpha deletion including the heart (PPARalpha-/-) to myocardial ischemia-reperfusion injury. Isolated working hearts from MHC-PPARalpha and nontransgenic (NTG) littermates were subjected to no-flow global ischemia followed by reperfusion. MHC-PPARalpha hearts had significantly higher FAO rates during aerobic and postischemic reperfusion (aerobic 1,479 +/- 171 vs. 699 +/- 117, reperfusion 1,062 +/- 214 vs. 601 +/- 70 nmol x g dry wt(-1) x min(-1); P < 0.05) and significantly lower glucose oxidation rates compared with NTG hearts (aerobic 225 +/- 36 vs. 1,563 +/- 165, reperfusion 402 +/- 54 vs. 1,758 +/- 165 nmol x g dry wt(-1) x min(-1); P < 0.05). In hearts from PPARalpha-/- mice, FAO was significantly lower during aerobic and reperfusion (aerobic 235 +/- 36 vs. 442 +/- 75, reperfusion 205 +/- 25 vs. 346 +/- 38 nmol x g dry wt(-1) x min(-1); P < 0.05) whereas glucose oxidation was significantly higher compared with wild-type (WT) hearts (aerobic 2,491 +/- 631 vs. 901 +/- 119, reperfusion 2,690 +/- 562 vs. 1,315 +/- 172 nmol x g dry wt(-1) x min(-1); P < 0.05). Increased FAO rates in MHC-PPARalpha hearts were associated with a markedly lower recovery of cardiac power (45 +/- 9% vs. 71 +/- 6% of preischemic levels in NTG hearts; P < 0.05). In contrast, the percent recovery of cardiac power of PPARalpha-/- hearts was not significantly different from that of WT hearts (80 +/- 8% vs. 75 +/- 9%). This study demonstrates that chronic activation of PPARalpha is detrimental to the cardiac recovery during reperfusion after ischemia.
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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) | 0.001 | 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 | 0.000 |
| 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".