Global REACH 2018: High Altitude-Related Circulating Extracellular Microvesicles Promote a Proinflammatory Endothelial Phenotype <i>In Vitro</i>
Bibliographic record
Abstract
Brewster, L. Madden, Anthony R. Bain, Vinicius P. Garcia, Noah M. DeSouza, Michael M. Tymko, Jared J. Greiner, and Philip N. Ainslie. Global REACH 2018: high altitude-related circulating extracellular microvesicles promote a proinflammatory endothelial phenotype in vitro . High Alt Med Biol . 24:223–229, 2023. Introduction: Ascent to high altitude (HA) can induce vascular dysfunction by promoting a proinflammatory endothelial phenotype. Circulating microvesicles (MVs) can mediate the vascular endothelium and inflammation. It is unclear whether HA-related MVs are associated with endothelial inflammation. Objectives: We tested the hypothesis that MVs derived from ascent to HA induce a proinflammatory endothelial phenotype. Methods: Ten healthy adults (8 M/2 F; age: 28 ± 2 years) residing at sea level (SL) were studied before and 4–6 days after rapid ascent to HA (4,300 m). MVs were isolated and enumerated from plasma by centrifugation and flow cytometry. Human umbilical vein endothelial cells were treated with MVs collected from each subject at SL (MV-SL) and at HA (MV-HA). Results: Circulating MV number significantly increased at HA (26,637 ± 3,315 vs. 19,388 ± 1,699). Although intracellular expression of total nuclear factor kappa beta (NF-κB; 83.4 ± 6.7 arbitrary units [AU] vs. 90.2 ± 6.9 AU) was not affected, MV-HA resulted in ∼55% higher ( p < 0.05) active NF-κB (129.6 ± 19.8 AU vs. 90.7 ± 10.5 AU) expression compared with MV-SL. In addition, MV-HA induced higher interleukin (IL)-6 (63.9 ± 3.9 pg/ml vs. 53.3 ± 3.6 pg/ml) and IL-8 (140.2 ± 3.6 pg/ml vs. 120.7 ± 3.8 pg/ml) release compared with MV-SL, which was blunted with NF-κB blockade. Conclusions: Circulating extracellular MVs increase at HA and induce endothelial inflammation, potentially contributing to altitude-related vascular dysfunction.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 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".