Abstract 623: Activating Liver X Receptors Alters Endothelial Progenitor Cell Differentiation and Enhances the Release of Factors that Reduce Atherosclerosis
Bibliographic record
Abstract
The liver x receptors (LXRα/β) are nuclear receptors that are highly expressed in macrophages and endothelial progenitor cells (EPCs). EPCs are bone marrow (BM) derived cells that facilitate endothelial repair through the secretion of factors. The importance of LXRs in preventing atherosclerosis has been attributed to promoting cholesterol efflux from macrophages. However, a role for EPCs in the LXR response has not been explored. We hypothesized that LXR activation in EPCs contributes to their anti-atherogenic effects by preventing endothelial activation during atherogenesis. In the Lxr -/- mice, circulating EPCs were decreased by 27% compared to WT, while myeloid populations were increased. Isolated hematopoietic stem cells treated with LXR agonist (1μM GW3965) ex vivo showed a 36% increase in the number of EPC colonies formed, while myeloid colonies were decreased by 25%. GW3965 treatment during EPC differentiation resulted in a 76% decrease in endothelial lineage marker ( Cd144 and Vegfr2 ) expression. To investigate endothelial cell activation, activated human umbilical vein endothelial cells were incubated with the conditioned media (CM) from GW3965-treated WT EPCs, which reduced THP-1 monocyte adhesion by 36% compared to the CM from vehicle treatment. To determine the effects of the EPC-derived CM in vivo , Ldlr -/- mice were injected with concentrated CM bi-weekly over an 8-week period, which decreased aortic sinus lesion area by 52% compared to the media control injections. Taken together, the loss of LXRs perturbed hematopoietic balance in vivo , while the activation of LXRs were associated with enhanced ex vivo EPC formation. Furthermore, LXR activation altered EPC differentiation and secretome resulting in decreased in vitro endothelial-monocyte adhesion. When administered to atherosclerotic-prone mice, these secreted factors reduced lesion formation in the aortic sinus. These data suggest that LXRs reduce the development of atherosclerosis in part through the release of EPC-derived factors that can reduce endothelial activation.
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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 | 0.001 |
| 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".