Abstract 16767: Exosomes Mediate Heat Shock Protein 27 Athero-Protective Signalling
Bibliographic record
Abstract
Introduction: Exosomes represent a discrete population of nano-vesicles secreted by a variety of cells and may contain unique protein cargo that play a role in inter-cellular signalling. We previously showed (ATVB 2009, JACC 2013) that membrane-like vesicles mediate the release of the novel biomarker and athero-protective agent, Heat Shock Protein 27 (HSP27), however did not explore downstream signalling effects of HSP27-laden exosomes. Hypothesis: Monocyte derived exosomes facilitate the transfer of HSP27 to human aortic endothelial cells (HAEC) and THP-1 MΦ to elicit athero-protective signalling effects. Methods: Exosome particles were purified from conditioned medium of THP-1 monocytes. As we previously showed that HSP27 athero-protection involves activation of NF-kB (e.g., with resultant changes in the expression of key athero-protective genes) we sought to determine if exosomes alter NF-kB signalling, as well as augment the internalization of HSP27 into cells as a cell membrane receptor for HSP27 is yet to be established. Results: Purified THP-1 derived exosomes express the classical exosome biomarkers CD81 and MHC-II. Flow cytometry revealed that 18% and 23% of these exosomes are positive for HSP27 immunolabeling with 10 and 40 μg/ml anti-Hsp27-FITC, respectively. The fraction of positive exosomes dropped to 3% when 40 μg/ml of recombinant HSP27 (rHSP27) was co-mixed with these samples and 10 μg/ml anti-HSP27-FITC, thereby confirming immunolabeling specificity. In contrast, a FITC labeled truncated form of the C-terminus of HSP27 (referred to as rC1-FITC) did not bind to exosomes. Indeed, exogenous rHSP27 bound to exosomes potentiated a ~50% increase of triggered NF-κB signalling (p<0.001) in THP-1 MΦ containing an alkaline phosphatase NF-kB reporter construct, while the truncated form of HSP27 (or rC1) did not (p=0.56). In both THP-1 MΦ and HAEC internalization of rHSP27-FITC into cells improved dramatically after exosome binding (e.g., THP-1: 157% increase, p<0.0001), while rC1-FITC had no effect. Conclusion: Exosomes contain HSP27 cargo that provide a novel inter-cellular signalling mechanism for the athero-protective effects of HSP27 by activating NF-kB and facilitating HSP27 internalization into cells.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.010 | 0.003 |
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".