MMP-2 INHIBITION ATTENUATES HYPERTENSIVE ECCENTRIC CARDIAC HYPERTROPHY AND DYSFUNCTION BY PRESERVING TROPONIN I AND DYSTROPHIN
Bibliographic record
Abstract
Objective: To verify wether increased matrix metalloproteinase (MMP)-2 activity contributes to the proteolysis of troponin I and dystrophin in the left ventricle (LV) of two kidney-one clip (2K1C) rats thus favoring the transition from concentric (C-LVH) to eccentric hypertrophy (E-LVH) and cardiac dysfunction. Design and method: Male 7-week old Wistar rats were sham or 2K1C operated and treated with water or doxycycline (MMP inhibitor, 15 mg/kg/day) by gavage from the tenth to the sixteenth week post-surgery. To establish this aim, tail-cuff plethysmography, echocardiogram, morphological analysis (collagen deposition and cardio myocyte hypertrophy assay), gelatin and in situ zymography, confocal microscopy of MMP-2 and troponin I, troponin I western blotting and mass spectrometry, and dystrophin in silico analysis and immunofluorescence were performed. Results were analyzed by two-way ANOVA or unpaired t test (Ethics Committee approval number: 023/2015-1). Results: All 2K1C rats had increased systolic blood pressure when compared to controls (p < 0.05) and doxycycline did not decrease it (p > 0.05). About 25% of 2K1C rats had E-LVH followed by reduced ejection fraction and fractional shortening (p < 0.05). The remaining had C-LVH with preserved cardiac function (p < 0.05). Doxycycline prevented the transition from C-LVH to E-LVH. Both C-LVH and E-LVH rats had cardio myocyte hypertrophy (p < 0.05) and doxycycline reverted it (p < 0.05). E-LVH was the only group who had more collagen deposition in the LV (p < 0.05). MMP-2 activity increased in C- and E-LVH hearts when compared to controls (p < 0.05) and doxycycline inhibited it (p < 0.05). MMP-2 and troponin I co-localize in the LV of control rats (p < 0.05). This was associated with an increase in troponin I cleavage products in E-LVH when compared to C-LVH (p < 0.05) confirmed by western blotting and mass spectrometry. Moreover, about ten putative MMP-2 cleavage sites in rat dystrophin were found and, in fact, a decline in dystrophin levels was observed in E-LVH when compared to controls (p < 0.05) which was prevented by doxycycline (p < 0.05). Conclusions: Hypertension causes increased cardiac MMP-2 activity which reduces both troponin I and dystrophin levels and contributes to the transition from C-LVH to E-LVH.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".