Abstract P526: MMP-2 Activation By S-glutathiolation Decreases Calponin-1 During Vascular Remodeling In Hypertension
Bibliographic record
Abstract
Aim: Antioxidant tempol may decrease MMP-2 activation by S-glutathiolation as it reduces oxidative stress, and then prevents calponin-1 cleavage and aortic remodeling in hypertension. Methods: Male Wistar rats were submitted to the two kidney-one clip (2K-1C) model of hypertension or sham surgery and were treated with tempol (18 mg/kg/day) or water by gavage for one week. Systolic blood pressure (SBP) was accessed by tail-cuff plethysmography. Aortas were used to perform in situ zymography, immunofluorescence for dihydroethidium and calponin-1, immunohistochemistry for nitrotyrosine, co-immunoprecipitation for glutathione followed by Western blot for MMP-2 and histomorphology. Two-way ANOVA followed by Bonferroni test was done (Ethics Committee approval number: 0015/2017). Results: SBP increased in 2K-1C rats compared to Sham group (156±2.9 vs. 128.6±4.1, p<0.05) and tempol did not reduce it (147.3±4.7, p>0.05). Morphological analysis showed increased that 2K-1C aortas had increased media to lumen ratio (M/L) (8.6±0.7 vs. 6.5±0.2) and cross-sectional area (CSA) (1.4x10 6 ±1.5x10 5 vs. 9.7x10 5 ±4.2x10 4 ) (p<0.05 vs. Sham), but tempol did not decrease them (M/L: 7.9±0.8; CSA: 1.3x10 6 ±1.3x10 5 , p>0.05 vs. 2K-1C). However, tempol decreased 2K-1C-induced increased nitrotyrosine levels (5.9x10 5 ±1.3x10 4 vs. 4.0x10 5 ±6.1x10 4 ), dihydroethidium (16.9±1.7 vs. 8.9±1.1) and MMP-2 activity (57.5±6.4 vs. 39.4±2.6; p<0.05). All four groups presented S-glutathiolation of MMP-2, however, the levels of calponin-1 were only reduced in aortas from 2K-1C rats (17.2±1.5 vs. 28.5±1.2, p<0.05 vs. Sham groups) and tempol reverted such loss (23.6±1.6, p<0.05 vs. 2K-1C). As calponin-1 is a potential intracellular target of MMP-2 in VSMC, these results suggest that the intracellular activation of MMP-2 may be more pronounced in hypertension. Different concentrations of tempol (0.5, 1 or 1.5 mM) did not directly inhibit MMP-2 activity in gelatin zymography (respectively: 4.6x10 6 ±7.4x10 4 , 4.9x10 6 ±1.2x10 5 and 4.8x10 6 ±1.5x10 5 vs. 4.6x10 6 ±2.2x10 5 ; p>0.05). Conclusion: Increased oxidative stress may contribute to activate aortic MMP-2 by S-glutathiolation in early hypertension, thus resulting in calponin-1 loss and maladaptive remodeling.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 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".