The role of aging on endothelial cell–cell junctions and pulmonary microvascular permeability in male mice
Bibliographic record
Abstract
Abstract Pulmonary microvascular endothelial cell (PMVEC) intercellular junctions are critical for maintaining barrier function and mitigating pulmonary edema. Previously, we demonstrated that aging exacerbated pulmonary microvascular permeability in a model of lung injury. Based on this, we hypothesized that aging was associated with increased PMVEC barrier dysfunction due to impaired cell–cell junction integrity. PMVEC were isolated from young and aged mice and cultured to confluence in vitro. Barrier function, junctional integrity, alterations in the proteome, markers of inflammation, and actin cytoskeleton organization were all assessed. To model injurious conditions, PMVEC were stimulated with inflammatory cytokines. PMVEC from aged mice exhibited increased permeability, both under basal and inflammatory conditions, which was associated with disrupted cell‐surface localization of the adherens junction protein, vascular endothelial (VE)‐cadherin. Protein abundance of VE‐cadherin was increased with age, while levels of the adapter protein, ‐catenin, and the tight junction protein, claudin‐5, were decreased. Measures of inflammation, including cytokine expression and cell surface abundance of adhesion molecules, did not differ with age. Augmented presence of actin stress fibers was observed in aged PMVEC. We conclude that aging predisposes PMVEC to elevated injury, due to inherent deficiencies in cell–cell junctions and barrier function, potentially mediated through altered actin cytoskeleton organization.
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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 | 0.000 | 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) | 0.000 | 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".