Abstract 1312: Dietary Supplementation With Sodium Valproate Attenuates Lesion Development In Hyperglycemic Apolipoprotein E-deficient Mice
Bibliographic record
Abstract
Diabetes mellitus is a major independent risk factor for cardiovascular disease and stroke however the molecular and cellular mechanisms by which diabetes contributes to the development of vascular disease are not fully understood. We have shown that conditions of hyperglycemia are associated with accumulation of glucosamine, a down stream metabolite of glucose, in specific cell types. Our findings indicate that elevated levels of intracellular glucosamine can promote endoplasmic reticulum (ER) stress in vascular cells leading to inflammation and lipid accumulation - the hallmark features of atherosclerosis. Treatment with valproic acid, a small branch chain fatty acid, can protect cultured cells from glucosamine-induced lipid accumulation by a mechanism that appears to involve inhibition of the signaling factor glycogen synthase kinase (GSK)-3. Here we evaluate the hypothesis that valproic acid can reduce the development and progression of atherosclerotic lesions in a hyperglycemic mouse model of accelerated atherosclerosis. Female apoE −/− mice were made hyperglycemic with multiple low dose injections of streptozotocin. At 15 weeks of age, hyperglycemic mice had accelerated the development of atherosclerotic lesions at the aortic root compared to normoglycemic mice. Mice fed a diet supplemented with 625 mg/kg sodium valproate had significantly reduced lesion volume relative to unsupplemented controls (4.98±0.76 versus 8.62±1.23 μm 3 , P <0.05, n =9). Valproate supplementation had no apparent effect on plasma glucose or plasma lipid levels or on the expression of diagnostic markers of ER stress in the atherosclerotic plaque. Significant reductions were observed in total hepatic lipids (>50.4%, P <0.05, n =3) and hepatic GSK-3β activity (>55.8%, P <0.05, n =3) in mice fed the valproate diet. In conclusion, dietary supplementation with low levels of sodium valproate significantly attenuates atherogenesis in hyperglycemic apoE −/− mice. This effect may involve the previously observed ability of valproate to attenuate the downstream effects of ER stress, such as GSK-3β activity.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".