TIMP‐1 protein but not secretion is increased by shear stress in the skeletal muscle microvasculature
Bibliographic record
Abstract
Luminal splitting is a form of angiogenesis caused by increased shear stress. A feature of luminal splitting is a lack of extracellular matrix proteolysis correlated with decreased production of matrix metalloproteinase (MMP)‐2. We hypothesized that an MMP inhibitor, tissue inhibitor of matrix metalloproteinase (TIMP)‐1, is upregulated by shear stress. TIMP‐1 mRNA increased in the EDL of prasozin‐treated rats (p<0.05, n=4) as measured by RT‐PCR. Rat skeletal muscle microvascular endothelial cells were exposed to shear stress (12 dyne/cm 2 ). TIMP‐1 mRNA increased in cells after 2 and 24 hours of shear (p<0.05, n=3), and TIMP‐1 protein increased at 2 and 24 but not 4 hours (p<0.05, n=3) as assessed by Western. TIMP‐1 secretion decreased at 2 hours of shear and returned to control levels at 24 hours (p<0.01, n=3) as measured by reverse zymography of concentrated media. Similarly, MMP‐2 activity increased in media at 2 but not 24 hours of shear (p<0.05, n=7) as assessed by an in vitro MMP‐2 activity assay (Anaspec). 2 hours of shear caused no change in TIMP‐1 surface staining (ns, n=3) as assessed by confocal microscopy, but did cause an increase in intracellular TIMP‐1 staining (p<0.05, n=3). Our results show that intracellular TIMP‐1 protein is increased by shear stress, due to increased production and decreased secretion. The function of intracellular TIMP‐1 is unknown. Funded by the Heart and Stroke Foundation of Canada. Grant Funding Source Heart and Stroke Foundation of Canada
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".