Methylglyoxal stimulated proliferation of vascular smooth muscle cell through enhanced cytoplasmic CDK2 activity
Bibliographic record
Abstract
Elevated MG levels and over‐proliferation of vascular smooth muscle cells (VSMCs) in spontaneously hypertensive rats has been reported. Present study investigated the effect of MG on VSMCs proliferation. Application of MG at the range of 0.01 to 10 μM significantly increased DNA synthesis and proliferation of cultured VSMCs, which was abolished by co‐application of N ‐acetylcysteine (NAC) or superoxide dismutase (SOD). Cyclin‐dependent kinase 2 (CDK2) activity in cytoplasmic fraction, but not nuclear fraction, of MG‐treated cells was increased, as compared with that of control cells. Activity of cyclin A‐CDK2 complexes, but not cyclin E‐CDK2, was responsible for the increased cytoplasmic CDK2 activity. Protein levels of CDK2, cyclin A, cyclin E and phosphorylation at residue Thr160 of CDK2 were not altered by MG treatment. However, phosphorylation at residue Tyr15 of CDK2 was significantly decreased in MG‐treated cells compared to control cells, which may account the increased cytoplasmic CDK2 activity. Increased cytoplasmic CDK2 activity and decreased phosphorylation on Tyr15 of CDK2 in MG‐treated cells were prevented by co‐application of NAC or SOD. In conclusion, MG at physiologically relevant concentrations stimulated VSMCs proliferation through an enhanced cytoplasmic CDK2 activity. Increased MG level, therefore, may underscore increased proliferation of VSMC in some cardiovascular disorders. (Grants from Canadian Institutes of Health Research (CIHR, MOP‐68938) and Heart and Stroke Foundation of Canada to L. Wu.)
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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".