EP 80317, a ligand of the CD36 scavenger receptor, protects apolipoprotein E‐deficient mice from developing atherosclerotic lesions
Bibliographic record
Abstract
CD36, a type B scavenger receptor expressed on macrophages, appears to play a major role in fatty streak formation through scavenging oxidatively modified lipoproteins in the arterial wall. We tested the hypothesis that EP 80317, a novel CD36 ligand derived from the growth hormone (GH)-releasing peptide family but devoided of any GH releasing activity, exerts anti-atherosclerotic effects in apolipoprotein E-deficient (apoE-/-) mice fed an atherogenic diet from 6 wk of age. Daily subcutaneous injections of EP 80317 (300 microg/kg) or vehicle were initiated at 6, 10, 12, or 14 wk until death at 18 wk. En face analyses of the entire aortic tree revealed a striking reduction (up to 51%) of lesion areas in EP 80317-treated apoE-/- mice compared with controls. Chronic treatment with EP 80317 (12 wk) is also associated with a 30% decrease in total plasma cholesterol, suggesting potential effects of this drug on cholesterol metabolism at the intestine/hepatic levels. EP 80317 exerts both preventive and curative effects on atherosclerotic lesion progression that were shown to be reversible after cessation of treatment. At the macrophage level, EP 80317 reduced oxidized low density lipoproteins internalization and up-regulated genes involved in cholesterol efflux, including peroxisome proliferator-activated receptor gamma (PPARgamma), liver x receptor alpha (LXRalpha), and the ATP binding cassette (ABC) transporters ABCA1 and ABCG1, supporting a role in regulating peripheral cholesterol trafficking. Importantly, the effects of EP 80317 were shown to be CD36 dependent, inasmuch as no anti-atherosclerotic or hypocholesterolemic effects were observed in apoE/CD36 double-deficient mice. In addition, long-term treatment of apoE/CD36 double-deficient mice with EP 80317 did not modulate the expression of genes of the PPARgamma-LXRalpha-ABC transporters pathway. Our results suggest that EP 80317, as a CD36 ligand, might be a prototype for a novel class of anti-atherosclerotic agents.
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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 | 0.001 | 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 | 0.001 |
| 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".