Abstract 274: Lipid Accumulation in CD11c-Expressing Intimal Myeloid Cells Induces Chemokine Production Required for Leukocyte Recruitment to Early Atherosclerotic Lesions
Bibliographic record
Abstract
Background: In the early stages atherosclerosis myeloid cells accumulate through the recruitment of circulating monocytes and macrophage proliferation. However, the first foam cells appear in the artery wall prior to increased monocyte recruitment and macrophage proliferation. These initial foam cells are derived from myeloid cells residing in the normal intima, and express integrin alpha X (CD11c). Rationale: When CD11c + cells were depleted at the initiation of a cholesterol-rich diet (CRD) in Ldlr -/- mice, lipid accumulation was reduced. We hypothesize that lipid accumulation in CD11c + intimal myeloid cells play an instrumental role in the recruitment of circulating monocytes to the artery wall. Methods: To assess the role if CD11c-expressing intimal myeloid cells in early atherosclerosis, CD11c + cells were deleted in Ldlr -/- mice reconstituted with bone marrow from CD11c-DTR transgenic mice. Mice reconstituted with C57BL/6 bone marrow were used as controls. Depletion of CD11c + cells was maintained throughout a 10 or 21 days CRD by giving injections of diphtheria toxin every three days. Monocyte recruitment was assayed by pulse labeling and quantifying BrdU positive leukocytes in the aortic arch. Intimal gene expression of adhesion molecules and chemokines was carried out by real-time PCR. Functional characterization of intimal chemokine expression on the recruitment of circulating monocytes was evaluated by antibody blockade of chemokine receptor CCR5 as well as reconstituting Ldlr -/- with CCL5 deficient bone marrow. Results: Recruitment of circulating monocytes was reduced in Ldlr-/- chimeras depleted of CD11c + cells. Correspondingly, intimal expression of chemokines CCL3, CCL4 and CCL5 were significantly blunted after 21 days of CRD in in Ldlr -/- BM chimeras depleted of CD11c + cells. The recruitment of BrdU labeled circulating monocytes was reduced by antibody blockade of CCR5 - the receptor for CCL3, CCL4 and CCL5. Conclusion: Collectively these data suggest that lipid accumulation in resident CD11c + intimal myeloid cells promote the recruitment of circulating monocytes to nascent lesions through the expression of CCL3, CCL4 and CCL5.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 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 | 0.001 |
| 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".