Abstract 534: Bone Marrow Transplantation Impacts the Earliest Stage of Atherosclerotic Lesion Formation
Bibliographic record
Abstract
Introduction: Bone marrow transplantation (BMT) is used to investigate the role of BM-derived cells in atherosclerosis. BMT promotes the formation of advanced atherosclerotic lesions in the aortic root of chimeric Ldlr -/- mice, whereas lesions formation in the aorta, including the lesser curvature of the aortic arch, is diminished. This phenomenon suggests distinct regional regulation of atherosclerotic lesion formation. The purpose of this study is to elucidate the mechanism(s) that reduce atherogenesis in the aortic arch of BMT mice, which would provide insights into how lesion grows and identify potential therapeutic targets of lesion initiation and progression. Methods and Results: Atherosclerosis was compared in non-irradiated Ldlr -/- mice to Ldlr -/- mice that underwent BMT at 6 wks of age (10 Gy whole body γ-irradiation and reconstitution with wild type (WT) BM). At 12 wks of age, mice were fed a cholesterol rich diet (CRD). Although body weight and total serum cholesterol levels were comparable between the groups, myeloid cell and lipid accumulation (en face immunoconfocal microscopy of CD68 and Oil Red O) in the lesser curvature of the aortic arch were dramatically reduced in the BMT group at 3, 6 and 12 wks of CRD. Apoptosis of myeloid cells (TUNEL + cells) was not increased in the BMT group, and lesion size at 6 wks was comparable in WT vs. CD11c- hBcl2 BMT mice. Myeloid cell proliferation in 3 wk lesions and monocyte recruitment (BrdU pulse labeling experiments) were significantly reduced in the BMT group, but comparable if normalized for lesion area. The accumulation of neutral lipid (Nile Red staining) in myeloid cells was significantly reduced in the BMT group at 5d of CRD. Conclusions: γ-irradiation and BMT suppresses atherogenesis from the earliest detectable stage - accumulation of lipid at 5d of CRD in resident myeloid cells in lesser curvature of ascending aortic arch. This suggests that irradiation reduces LDL entry into the intima possibly by altering endothelial cell (EC) transcytosis. We established an approach to isolate RNA from immuno-purified ECs microdissected from intima, which enables assessment of genes implicated in LDL transcytosis, and are developing assays to directly assess LDL transcytosis in early lesions.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".