Abstract 455: The Effects of Diet on Occlusive Coronary Artery Atherosclerosis, Thrombosis and Myocardial Infarction in SR-BI/LDL Receptor Double KO Mice
Bibliographic record
Abstract
Objective: Deficiency of the HDL receptor, SR-BI, in apolipoprotein E knockout or hypomorphic mice respectively results in spontaneous or diet-inducible occlusive coronary artery atherosclerosis, myocardial infarction, and early death. Here, we examine the effects of SR-BI deficiency on cardiovascular phenotypes in LDLR knockout mice fed different atherogenic diets. Approach and Results SR-BI/LDLR double knockout and control LDLR knockout mice were fed diets containing different amounts of fat and cholesterol and which either lacked or contained 0.5% sodium cholate. Double knockout mice fed diets high in cholesterol exhibited significantly reduced survival compared to LDLR knockout mice fed the same diets. In addition to increased aortic sinus atherosclerosis, we observed significant coronary artery atherosclerosis in double knockout mice, and diet dependent accumulation of platelets in coronary artery atherosclerotic plaques. This was accompanied by substantial myocardial fibrosis in double knockout mice fed high cholesterol diets. Double knockout mice also exhibited higher circulating cytokine levels, monocytosis with increased proportions of monocytes expressing high levels of Ly6C, and higher adhesion molecule expression in coronary artery endothelial cells compared to control LDLR knockout mice. Conclusions: Diet accelerated atherosclerosis and occlusive, platelet rich coronary artery disease in SR-BI/LDLR dKO mice is affected by amounts of cholesterol and cholate in atherogenic diets, and is accompanied by increased expression of VCAM-1 and ICAM-1 in coronary arteries and increased Ly6C+ monocytes in circulation. The increased VCAM-1 and ICAM-1 in coronary artery endothelial cells in SR-BI-deficient mice likely explains their increased susceptibility to atherosclerosis in coronary arteries.
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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".