Plasma Exosomes and Improvements in Endothelial Function by Angiotensin 2 Type 1 Receptor or Cyclooxygenase 2 Blockade following Intermittent Hypoxia
Bibliographic record
Abstract
Intermittent hypoxia (IH) is associated with increased endothelial dysfunction and cardiovascular disorders. Exosomes released in biological fluids may act as vehicles for propagating such damage, modifying the functional phenotype of endothelial cells. Drug interventions, however, may provide protection for the endothelium, in spite of exosomal activity. Using an experimental human model of IH, we investigated whether the beneficial effects of two drugs, Celecoxib (CEL) and Losartan (LOS), on IH-induced vascular dysfunction was mediated via exosomes or independent of IH-induced exosomal cargo alterations. We hypothesized that the beneficial effects of Celecoxib (CEL) and Losartan (LOS) on IH-induced vascular dysfunction would be mediated via modifications of exosomal properties by the drugs, rather than by direct effects of the drugs on the endothelium. Ten male volunteers were exposed to IH (single exposure of 6 h) while receiving LOS, CEL, or placebo (P) for 4 days before IH exposures, and plasma samples were obtained from which exosomes were isolated, and incubated with naïve human endothelial cell cultures either not treated or pre-treated with LOS, CEL, or placebo (P). Functional reporter assays (monolayer impedance, monocyte adhesion, eNOS phosphorylation) revealed that the degree of exosome-induced endothelial dysfunction was similar among IH-exposed subjects independent of drug treatment. However, pre-treatment of naïve endothelial cells with LOS or CEL before addition of exosomes from IH-exposed subjects afforded significant protection. Thus, the cardiovascular protective impact of LOS and CEL appears to be mediated by their direct effects on endothelial cells, rather than via modulation of exosomal cargo.
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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) | 0.001 | 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 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".