Abstract 284: A Deficiency in the HDL Receptor SR-BI Attenuates Atherosclerotic Plaque Regression in ApoE-Hypomorphic Mice
Bibliographic record
Abstract
A deficiency in the HDL receptor, SR-BI, results in accelerated arterial plaque development in ApoE-R61 hypomorphic (“Hypo-E”) mice, however the effect of a lack of SR-BI on atherosclerotic plaque regression is unknown.To explore the role of SR-BI in the regression of arterial atherosclerosis in the Hypo-E mouse model, SR-BI-deficient/Hypo-E (SR-BI-deficient) or SR-BI-expressing/Hypo-E (control) mice were fed high-cholesterol, high-fat diets (HFD) for either 4 or 11weeks (w) to induce the formation of atherosclerotic plaques of similar size in the aortic sinus. The mice were then switched to a normal chow diet (NCD) for 11 w. As had been shown previously by others, atherosclerotic plaques in control mice regressed almost completely during the 11 w of NCD feeding. In contrast, atherosclerotic plaques in SR-BI-deficient mice did not undergo regression but rather continued to grow in size after the switch from HFD to NCD. Concomitantly, circulatory cytokines (IL-6 and TNF-alpha) and atherogenic lipoproteins were elevated by HFD feeding in both groups, and returned to basal levels in control mice, but remained elevated in SR-BI-deficient mice after the switch from HFD to NCD. Immunofluorescence analyses revealed that CD11c-positive dendritic cells were retained in the plaques of SR-BI-deficient Hypo-E mice, which exhibited apparently attenuated expression of CCR7. In a separate experiment SR-BI-deficient mice were fed HFD for 4 weeks and then switched to NCD without or with 0.5% probucol. In untreated group, atherogenic lipoproteins remained elevated and plaques continued to grow after the switch from HFD to NCD, tripling in size by 8 weeks. Probucol treatment resulted in reduced levels of VLDL and LDL cholesterol and halted further lesion growth but did not trigger plaque regression. Probucol treatment was, however, accompanied by a decrease in CD11c staining in atherosclerotic plaques when compared to mice fed HFD for 4 weeks alone or followed by a further 8 weeks of NCD. Probucol also decreased expression of VCAM-1 in coronary arteries. These findings suggest that atherosclerotic plaque regression is impaired in SR-BI deficient mice. Probucol was able to halt further plaque growth but did not trigger plaque regression in SR-BI deficient hypo-E mice.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".