Abstract 520: Chronic Overexpression of Heat Shock Protein 27 Facilitates Favorable Plaque Remodeling?
Bibliographic record
Abstract
Background: Previously, we discovered that over-expression of Heat Shock Protein 27 (HSP27) in atherosclerosis-prone apoE -/- mice (apoE -/- HSP27 o/e ) maintained on a high fat diet (HFD) for 4 weeks reduces aortic lesion area - however, only in females. Purpose/Objective: To determine if chronic HSP27 over-expression modulates plaque lesion characteristics including aortic mechanical properties. Methods/Results: Male and female apoE -/- and apoE -/- HSP27 o/e mice fed a high fat diet for 12 weeks were studied. Relative to apoE -/- mice, female apoE -/- HSP27 o/e mice had aortic lesion area reductions of 35% for en face and 30% for cross-sectional sinus tissue sections. Interestingly, the same parameters were also reduced by 21% and 24%, respectively, in male cohorts. Aortic plaques from apoE -/- HSP27 o/e mice showed almost 50% reductions in the area occupied by cholesterol clefts and free cholesterol, with fewer macrophages and reduced macrophage apoptosis. The mechanical properties of the aorta were studied ex vivo using 2-mm vessel segments (n=14-20/group). We developed an apparatus to determine vessel stiffness during radial stretching at a constant rate, recording tension via a force transducer. There was an increase in vessel stiffness in apoE -/- HSP27 o/e mice compare to apoE -/- (female: 628±30Pa vs 444±38Pa, p<0.001; male: 679±19Pa vs 505±22Pa; p<0.001). The vasoactive response of aortic segments (n=12/group) to phenylephrine (PE), carbachol (CCh) and sodium nitroprusside (SNP) were also determined. While the vasorelaxation response induced by CCh and SNP were similar between the two animal groups, PE (10μM) produced a greater increase in vasoconstriction in apoE -/- HSP27 o/e mice compared to apoE -/- (female: 205±9% vs 162±10%, p<0.001; male: 190±9% vs 139±12%, p<0.01). Conclusion: Chronic over-expression of HSP27 provides a persistent atheroprotective effect that benefits both sexes and coincides with remarkable reductions in lesion cholesterol accumulation as well as macrophage apoptosis. In addition, it increases the aortic stiffness and the vasoactive response to PE in apoE -/- mice model. These data provide new clues as to how HSP27 may improve atherosclerotic lesion stability.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".