Abstract 5460 Heat Shock Protein 27 Over-Expression in Hematopoietic Cells is Atheroprotective and Anti-Inflammatory
Bibliographic record
Abstract
Previously, we demonstrated that Heat shock protein 27 (HSP27) shows diminished expression with progression of human coronary atherosclerosis [ATVB 2005]. Moreover, we have shown that global over-expression of HSP27 (HSP27 o/e ) protects against the development of atherosclerosis in ApoE −/− mice in part via binding to Scavenger Receptor-A [Circ Res 2008]. More recent experiments reveal that macrophage apoptosis is less frequent in advanced (12 wk) lesions from apoE −/− HSP27 o/e mice and highlight macrophage specific anti-inflammatory protective mechanisms. The purpose of this study was to determine if blood-borne cells (e.g., mononuclear cells) are sufficient and required for the HSP27 atheroprotective phenotype in female ApoE −/− mice. Methods/Results: Female ApoE −/− mice (~10 Weeks old and ≥ 18.5 g), underwent μ -irradiation to eliminate endogenous bone marrow before receiving bone marrow from either female ApoE −/− or ApoE −/− HSP27 o/e donors. After 6 weeks of recovery recipients were placed on a high fat/cholesterol diet for 4 weeks to induce atherosclerosis before being euthanized. ApoE −/− mice receiving bone marrow from ApoE −/− HSP27 o/e had detectable levels of HSP27 mRNA in liver and spleen. In addition, the HA tag of the over-expression construct was detectable in liver sections and HSP27 was measured in the serum from mice receiving the ApoE −/− HSP27 o/e bone marrow. Over-expression of HSP27 in cells of hematopoietic origin resulted in a 52% reduction in aortic en face lesion burden (p=0.005) and a 32% reduction in the lesion area found in aortic sinus cross-sections (p=0.02). The macrophage content of lesions in both murine populations was similar. In vitro bone marrow derived macrophages from ApoE −/− HSP27 o/e mice had a 2.7-fold decrease in oxidized LDL uptake after 24 hrs (p=0.002) and were less adherent to LPS activated HUVECs (p<0.05) when compared to ApoE −/− derived macrophages. In conclusion, the over-expression of HSP27 in bone marrow derived cells is sufficient and necessary to provide atheroprotection in ApoE −/− mice and points to a central role for HSP27 in reducing the inflammatory milieu of atherosclerotic 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) | 0.000 | 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) | 0.008 | 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".