Abstract 155: Contribution of Foamy Monocytes to Nascent Atherosclerosis
Bibliographic record
Abstract
Infiltration of monocytes into the arterial wall and subsequent differentiation into macrophages, which take up lipoproteins to become foam cells, is a key step in atherogenesis. We reported that apoE -/- mice on high fat diet (HFD) for 12 weeks had foamy monocytes, characterized as intracellular lipid droplets, in blood. However, atherosclerosis starts early in apoE -/- mice after HFD, and it is unknown when foamy monocytes first appear in blood of apoE-/-mice after HFD and whether foamy monocytes contribute to nascent atherosclerosis. In the current study, apoE -/- and wild-type (WT) mice were fed HFD or normal diet (ND) for 1-5 weeks. Monocyte numbers increased in apoE -/- mice from 1 week on HFD. Importantly, foamy monocytes began appearing in blood of apoE -/- mice within 1 week on HFD. The proportion of foamy to total monocytes increased from ~20% at 1 week to ~40% at 5 weeks on HFD. The majority (~85%) of foamy monocytes were CD11c + while the majority of nonfoamy monocytes were CD11c - in apoE -/- mice on HFD. Foamy monocytes also expressed higher levels of TNF-α and scavenger receptors including CD36 and CD204 than nonfoamy monocytes. Cholesteryl-ester-rich VLDL were isolated from apoE -/- mice on HFD, labeled with DiI and intravenously injected into apoE-/- mice on ND (recipients). At 3 hours post injection, both CD11c + and CD11c - monocytes in recipients took up VLDL, becoming DiI + . At 24 hours post injection, ~95% of the DiI + monocytes became CD11c + , suggesting that VLDL uptake, which would cause foamy monocyte formation, induced monocyte phenotypic change to CD11c + . Along with the early appearance of CD11c + foamy monocytes, atherosclerosis started early in apoE -/- mice on HFD. Proportions of CD11c + /CD11b + cells examined by flow cytometry and mRNA levels of CD11c and inflammatory markers such as IL-6 and IL-1β increased in aorta of apoE -/- mice within 3 weeks on HFD compared to those of apoE -/- mice on ND or of WT on ND or HFD. In vitro assay revealed that foamy monocytes adhered more avidly to VCAM-1 under fluid shear stress. In summary, appearance of foamy monocytes and aortic atherosclerotic lesions began early in apoE -/- mice fed HFD. Foamy monocytes may contribute to nascent atherosclerosis via infiltration into arterial wall and production of inflammatory markers.
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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) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".