Abstract 19004: Sr-bi Deficiency is Associated with Dendritic Cell Retention in Arterial Atherosclerotic Plagues and Impaired Atherosclerotic Regression in Apoe-r61 Hypomorphic Mice
Bibliographic record
Abstract
A deficiency in SR-BI, a major HDL receptor, results in accelerated arterial plaque development in ApoE-R61 hypomorphic mice, however the effect of a lack of SR-BI on atherosclerotic plaque regression is unknown. In SR-BI-knockout/ApoE hypomorphic (KO-H ) mice fed a high fat diet, aortic atherosclerosis developed much faster than in the SR-BI+/+ ApoE hypomorphic (control) mice. When these mice were switched from the atherogenic diet back to a normal diet, atherosclerotic plaques regressed over the course of 11 weeks in the control mice, but not in KO-H mice, in which the plaques continued to develop. Dendritic cells (DC's) have been found to be involved in atherosclerosis development and regression. Immunohistofluorescence analysis revealed a large number of CD11c-positive DC’s which persisted within atherosclerotic lesions of KO-H mice, even 11 weeks after the diet switching. These CD11c-positive cells exhibited apparently attenuated expression of CCR7, a major chemoattractant receptor in DCs. To determine if SR-BI in macrophages or DC’s themselves might be required for plaque regression, bone marrow (BM) was transplanted from either KO-H or control donors into irradiated ApoE-hypomorphic recipients. Plaque regression was decreased in the mice transplanted with BM from KO-H donors, confirming a role for SR-BI in BM-derived cells in plaque regression. In cultured human DC's derived from THP-1 cells, HDL dose-dependently stimulated migration. HDL-stimulated migration of DC's was abolished by a SR-BI blocking antibody, PI 3-kinase inhibitors or using BM-derived DC's from SR-BI or PDZK1 KO mice, suggesting the involvement of an HDL-triggered PI3K signaling pathway emanating from SR-BI and its cytosolic adaptor protein PDZK1. Cholesterol loading of DCs impaired migration in response to HDL or CCL19, a ligand for CCR7; this was reversed by overnight incubation with HDL. Furthermore, incubation with HDL for 24 h induced a remarkable increase in expression of CCR7 and SR-BI in DC's. Taken together, the results suggest that SR-BI may mediate the migration of DC's facilitated by HDL, and is required for atherosclerotic plaque regression.
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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| 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 | 0.002 |
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".