Inhibition of matrix metalloproteinase (MMP)‐dependent epidermal growth factor receptor (EGFR) transactivation prevents the development of hypertension in high fructose diet fed rats
Bibliographic record
Abstract
The metabolic syndrome is a cluster of cardiovascular risk factors among which are insulin resistance (IR) and hypertension. Despite major research efforts, it remains uncertain what causes the hypertension. Recent studies have suggested a link between disease progression and activation of growth factor receptor signaling pathways. A key event in this pathway is transactivation of growth factor receptors, such as the EGFR by MMPs. This transactivation can be triggered by agonists such as catecholamines, endothelin‐I and angiotensin II, all of which are elevated in models of hypertension including high fructose diet fed rats. We hypothesize that the increased activity of MMPs (MMP‐7) and subsequent transactivation of the EGFR contributes to the development of hypertension in high fructose diet fed rats. Male Wistar rats were fed with either normal rat chow or a 60% fructose diet for 10 weeks and treated daily with doxycycline (MMP inhibitor, 20 mg/kg) and AG 1478 (EGFR inhibitor, 5 mg/kg) orally for 4 weeks. Fructose fed rats developed IR, endothelial dysfunction and hypertension. Western and substrate zymographic analysis indicated increased expression and activity of MMP‐7 in cardiovascular tissues of untreated fructose rats. Inhibition of either MMP or the EGFR activity prevented endothelial dysfunction and development of hypertension without affecting IR. Our results suggest that the MMP‐EGFR pathway may be a potential target for the treatment of hypertension in metabolic syndrome. Funded by HSFC, CIHR & MSFHR.
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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 | 0.000 |
| 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) | 0.002 | 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".