Abstract 337: Extensive Coronary Artery Atherosclerosis and Myocardial Infarction in SR-BI/LDLR Double Knockout Mice Fed 4 Different Atherogenic Diets
Bibliographic record
Abstract
Mice lacking the HDL receptor, SR-BI, are susceptible to spontaneous or diet-inducible occlusive coronary artery (CA) atherosclerosis and myocardial infarction (MI) in the context of an absence, or mutated form of apoE, respectively. We tested the effects of SR-BI deficiency on aortic sinus and CA atherosclerosis in LDL receptor deficient mice fed four different atherogenic diets; the HFCC and HFC diets are composed of 15% fat, 1.25% cholesterol and either contain or lack 0.5% sodium cholate, respectively, the HC diet is a normal chow diet supplemented with 2% cholesterol, and the western diet contains 21% butter fat and 0.15% cholesterol. SR-BI/LDLR double knockout (dKO) mice fed the HFCC and HFC diets exhibited reduced survival; average survival was 3.5 and 9.5 weeks, respectively. Reduced survival was not observed in LDLR single knockout (sKO) control mice. Plasma lipoprotein cholesterol levels and triglyercide secretion rates were lower in dKO mice compared to sKO mice. Conversely, dKO mice developed significantly larger atherosclerotic plaques in their aortic sinuses compared to sKO mice, and severe occlusive CA atherosclerosis which was not observed in sKO mice. DKO mice fed the HC diet or western diet did not exhibit reduced survival up to 12 weeks of feeding, however CA atherosclerosis was still observed. CA atherosclerosis was accompanied by platelet positive staining and myocardial fibrosis, indicating MI. CA plaques in dKO mice were characterized by the presence of collagen and both CD68 and smooth muscle actin positive staining, indicating complex fibrous plaques consisting of both macrophages and smooth muscle cells. Plaque free CAs and CAs containing small, non-occlusive plaques stained positive for markers of activated endothelium. Importantly, dKO mice fed the HC diet had largest burden of atherosclerosis in their aortic sinuses whereas the extent of atherosclerosis in their CAs was the mild in comparison to that observed dKO mice fed the HFCC and HFC diets. This observation suggests that the development of atherosclerosis in the CAs and the aortic sinus are influenced by different factors.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".