Contributions of endothelin‐1 and sodium hydrogen exchanger‐1 in the diabetic myocardium
Bibliographic record
Abstract
BACKGROUND: Endothelin-1 (ET-1) and sodium hydrogen exchanger-1 (NHE-1) are important mediators of several disease processes affecting the heart, especially relating to myocardial ischemia. There is evidence that their actions may be interrelated. Their contributions to diabetic heart disease have not been extensively documented. Accordingly, the aim of this study was to investigate the interactive roles of ET-1 and NHE-1 in the pathogenesis of diabetic cardiomyopathy, a significant cause of morbidity in diabetic patients. METHODS: Streptozotocin-induced diabetic Sprague Dawley rats were treated with NHE-1 blocker cariporide or dual ET(A)/ET(B) blocker bosentan and were subsequently studied one, three and six months after induction of diabetes. These animals were compared with nondiabetic rats as well as with diabetic rats on poor blood glucose control. RESULTS: Diabetes leads to hyperglycemia, reduced body weight gain and increased glycated hemoglobin levels. These animals exhibited focal myocardial fibrosis and increased ejection fraction, in association with a tendency to increased left ventricular wall thickness and heart weight, after six months of follow-up, both bosentan and cariporide prevented these responses. Diabetes also caused significant increases in ET-1 mRNA and protein expression in the heart at all time points, which was further augmented by cariporide treatment for three months. Diabetes did not affect either mRNA or protein expression of NHE-1, although these did decrease in hearts of diabetic animals treated with bosentan for six months. CONCLUSIONS: These results indicate an important contribution of both ET-1 and NHE-1 in the pathogenesis of diabetic cardiomyopathy. These data suggest that NHE-1 may act as a downstream mediator in the production of ET-induced functional and structural changes in the myocardium in diabetes.
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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 | 0.002 | 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".