Abstract 544: Extracellular Heat Shock Protein 27 Inhibits Foam Cell Formation by Targeting Scavenger Receptor-A in the Vessel Wall
Bibliographic record
Abstract
Background: We showed that injection of recombinant heat shock protein 27 (rHSP27) into ApoE -/- mice reduces atherosclerosis lesions and total serum cholesterol levels. Extracellular HSP27 also interacts with scavenger receptor (SR)-A and inhibits acLDL uptake in macrophages, but the role of SR-A in HSP27 atheroprotection remains unclear. Purpose: To elucidate the mechanism of HSP27 atheroprotection by exploring if the presence of SR-A is required to facilitate its salutary effects. Methods/Results: rHSP27 treatment of bone-marrow derived macrophages from ApoE -/- mice reduced acLDL uptake (38%, p<0.05) using flow cytometry - effects not observed (p=0.171) in cells from ApoE -/- SR-A -/- mice. rHSP27 reduced acLDL binding (38%, p<0.01) and uptake (34%, p<0.01) in THP-1 macrophages associated with downregulation of SR-A transcript (46%, p<0.01) and total protein levels (63%, p<0.001). Flow cytometry and confocal microscopy revealed reduction in SR-A expression at the cell surface. To explore the signaling involved, NF-kB activation was assessed in THP-1 cells stably transfected with an NF-kB reporter. rHSP27 increased NF-kB activity (7 fold, p<0.001) and induced translocation of the NF-kB p65 subunit from the cytosol to the nucleus - effects that were inhibited (p<0.05) by the NF-kB antagonist, BAY. Addition of BAY inhibited the effect of rHSP27 on SR-A gene and protein expression and acLDL uptake (p<0.05). To explore the importance of SR-A in HSP27 atheroprotection, rHSP25 (mouse homologue) or PBS was administered to ApoE -/- and ApoE -/- SR-A -/- mice for 3 weeks on a high fat diet. Treatment of ApoE -/- mice revealed reductions of en face aortic lesions (39%, p<0.001), SR-A expression in the intima, and total serum cholesterol levels (32%, p<0.01). In the absence of SR-A, HSP27 atheroprotection was abolished (p=0.79) despite similar decreases in serum cholesterol levels (25%, p<0.05). Conclusions: Extracellular HSP27 inhibits foam cells by downregulating SR-A expression via an NF-κB-dependent mechanism. HSP27 atheroprotection requires the presence of SR-A expression in vivo. In the absence of SR-A, loss of atheroprotection occurs despite reductions in total serum cholesterol levels, suggesting SR-A as a novel target for HSP27 in the vessel wall.
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 | 0.001 |
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".