The structural integrity of the glycocalyx is compromised under inflammatory conditions on cultured ECs through the activation of MMP-2 under flow
Bibliographic record
Abstract
The glycocalyx covers the luminal surface of endothelial cells (ECs) and is important in several endothelial cell functions. Shedding of the glycocalyx occurs with vascular pathologies in whichEC dysfunction and inflammation are driving forces. In the current study, we investigated the structure of the glycocalyx on the surface of cultured human abdominal aortic ECs (HAAECs) inresponse to the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α), and under steady uniform laminar shear stress (LSS; 10 dynes/cm2 ) for 24 hours. We found a significant reduction in the expression of both heparan sulfate (~25%, p<0.01) and Syndecan-1 (~6%, p<0.05) with TNF-α and flow. The effects of TNF-α on glycocalyx damage were abrogated by the metalloproteinase inhibitor (MMP), GM6001. Under the same conditions we also observed a significant up-regulation in MMP-2 protein expression and activity. Enzymatic degradation of heparan sulfate alone can lead to a similar cell phenotype with an up-regulation of MMP-2 protein and activity. These findings demonstrate that the structural integrity of the glycocalyx is compromised on the surface of ECs under inflammatory conditions in an MMP-2-dependent manner, which may underlie EC dysfunction during inflammatory diseases such as atherosclerosis.
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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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".