Abstract 643: Absence of Four-and-a-Half LIM Domain Protein 2 Decreases Atherosclerosis in ApoE-/- Mice: Role of Monocytic Immune Cells
Bibliographic record
Abstract
Four-and-a-half LIM domain protein-2 (FHL2) is expressed in endothelial and vascular smooth muscle cells. It negatively regulates endothelial cell survival and migration, but its role in atherogenesis is unknown. To investigate the role of FHL2 in atherosclerosis, FHL2-deficient (FHL2-/-) mice were crossed with ApoE-deficient (ApoE -/-) mice, to generate ApoE/FHL2-/- mice. After 7 weeks of high fat diet, ApoE/FHL2-/- mice had significantly smaller (P<0.05) atherosclerotic plaques than ApoE-/- mice in the aortic sinus (0.14±0.02 vs. 0.29±0.04 mm2), the brachiocephalic artery (0.03±0.008 vs. 0.07±0.01 mm2) and the aorta (6.9±0.9 vs 10.3±1%), assessed by oil red O staining. This was associated with enhanced collagen (16±2 vs 8.6±3 %) and smooth muscle cell (4.5±0.8 vs 1.8±0.5%) contents within the plaques of ApoE/FHL-2-/- mice. Moreover, macrophage content within plaques was reduced 2-fold in ApoE/FHL2-/- vs ApoE-/- mice (P<0.05). This could be explained, in part, by the 40% reduction in aortic ICAM-1 mRNA and 55% reduction in VCAM-1 protein expression in the plaque. Furthermore, aortic gene expression of Cx3cl1 and Ccl5 was increased in ApoE/FHL2-/- vs ApoE-/- mice, suggesting that different monocyte populations might be recruited to the plaques. Peritoneal thioglycollate injection elicited equivalent numbers of monocytes and macrophages in both groups, but a significantly lower number of pro-inflammatory Ly6C high monocytes were recruited in ApoE/FHL2-/- vs ApoE-/- mice (8±3 vs 18±4%). Furthermore, mRNA levels of Cx3cr1 were 2-fold higher in monocytes from ApoE/FHL2-/- mice compared with ApoE-/- mice. Finally, we also investigated the potential importance of myeloid cell FHL2 deficiency in atherosclerosis. ApoE-/- or ApoE/FHL2-/- mice were lethally irradiated and transplanted with ApoE-/- or ApoE/FHL2-/- bone marrow. After recovery and 7 weeks of high fat diet, both chimeric groups developed smaller plaques than ApoE-/- mice transplanted with ApoE-/- bone marrow. These results suggest that FHL2 in both myeloid and vascular cells may play an important role in atherosclerosis by promoting pro-inflammatory chemokine production, adhesion molecule expression, and pro-inflammatory monocyte recruitment.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".