P531Mitochondria of parental cells control the capacity of monocyte-derived microvesicles to activate endothelial cells
Bibliographic record
Abstract
Funding Acknowledgements: FWF: SFB-54 "InThro" and CCHD (Cell Communication in Health and Disease) Introduction: Microvesicles (MVs) are recognized as mediators of inflammation and increased numbers of MVs have been described in cardiovascular diseases. Mitochondrial content has been shown to be present in MVs and to promote pro-inflammatory responses. However, the role of mitochondria in the MV-mediated pro-inflammatory communication between monocytes and endothelial cells is unknown. Purpose: To elucidate the contribution of mitochondria to the biological activity of monocyte-derived MVs on endothelial cells. Methods: MVs were isolated from conditioned media of THP-1 monocytes or plasma by differential centrifugation, characterized by flow-cytometry and qPCR and their ability to activate human umbilical vein endothelial cells (HUVECs) was tested. Results: LPS-stimulation of monocytes induced the release of MVs enriched in mitochondrial content as demonstrated by flow cytometry and quantitative PCR. Stimulation of endothelial cells with these MVs potently induced the expression of VCAM-1 and ICAM mRNA and IL-8 protein in endothelial cells. Disintegration of MVs by sonication did not alter this activity, indicating that MV integrity is not required to mediate these effects. However, the pro-inflammatory potential of MVs was drastically reduced when MVs were derived from monocytes with non-respiring mitochondria or monocytes cultured in the presence of pyruvate. MVs released by cells treated with the mitochondrial ROS scavenger MitoTEMPO had a reduced pro-inflammatory potential. Thus, the ability of MVs to monocyte-derived MVs to activate endothelial cells depends on the mitochondrial function of MV-shedding cells. Moreover, even mitochondria alone isolated from LPS-stimulated, but not from unstimulated cells, were able to activate endothelial cells.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".