Abstract 33: Atorvastatin Downregulates Vascular Nox Expression and Ameliorates Oxidative Stress-associated Inflammatory Process in Type 2 Diabetic Db/db Mice
Bibliographic record
Abstract
Nox-derived reactive oxygen species generation plays a role in endothelial dysfunction and vascular inflammation, which underline vascular damage observed in diabetes. Increasing evidence indicates that the beneficial effects of atorvastatin are associated with antioxidant mechanisms. We tested the hypothesis that atorvastatin influences Nox isoforms expression and ameliorates diabetes-associated vascular inflammation and redox signalling. Diabetic mice (db/db model of obesity and diabetes type II) and their control counterparts (db/+) were treated with atorvastatin (10 mg/Kg/day, p.o., 2 weeks). No differences were observed in BP among the groups. Improved oral glucose tolerance was observed in atorvastatin-treated db/db group (area under curve, db/db: 2858 ± 81 vs db/db atorvastatin: 2251 ± 158). Atorvastatin lowered plasma thiobarbituric acid-reacting substances levels in db/db mice (db/+: 4,7 ± 0,7 ;db/db: 6,5 ± 1,1 vs db/db atorvastatin: 4,9 ± 0,5 ). Increased expression of Nox1, 2 and 4 (1 to 3 fold increase vs db/+) and the associated enhance of ROS generation in the vasculature of db/db mice (db/+: 4312 ± 874; db/db: 27828 ± 8215 vs db/db atorvastatin: 8742 ± 2393 RLU) were abrogated by atorvastatin. The increase of vascular p47phox and RAC1/2 membrane translocation observed in db/db mice was also inhibited by atorvastatin. Diabetes-associated increase of VCAM-1 expression, NFkB p65 phosphorylation, and vascular monocyte adhesion were reduced by aotrvastatin treatment. Higher MAP kinase phophorylation levels observed in db/db mice were blunted by atorvastatin. Impaired vascular responses to acetylcholine (maxium effect %; db/+: 83 ± 5,1 ;db/db: 48 ± 6,4 vs db/db atorvastatin: 75 ± 5,2) and insulin (maxium effect %; db/+: 103 ± 7,5 ;db/db: 47 ± 2,0 vs db/db atorvastatin: 95 ± 7,1) in db/db mice were normalized by atorvastatin treatment. Our results demontrate that atorvastatin ameliorates oxidative stress and inflammatory process in db/db mice. Findings from this study identify NADPH oxidase as a target for atorvastatin. We describe novel mechanisms whereby statins may improve vascular function in obesity-associated diabetes.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 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) | 0.004 | 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".