Matrix metalloproteinase in the cardiovascular remodeling of hypertension: current insights and therapeutic potential
Bibliographic record
Abstract
Matrix metalloproteinase in the cardiovascular remodeling of hypertension: current insights and therapeutic potential Juliana M Parente, Michele M Castro Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil Abstract: Hypertension induces maladaptive vascular and cardiac remodeling, which are related to rearrangement of the extracellular matrix (ECM) and cell hypertrophy and migration. Matrix metalloproteinases (MMPs) are zinc-dependent proteases involved in tissue remodeling mainly by the proteolysis of ECM components. Increased MMP-2 activity is also involved in the proteolysis of important intracellular targets in cardiomyocytes and vascular smooth muscle cells (VSMC). Troponin I and calponin-1 are some of the targets of MMP-2 in cardiomyocytes and VSMC, respectively, that when degraded contribute to contractile dysfunction, cell hypertrophy or migration. MMP-2 may be activated by S-glutathiolation in vitro by peroxynitrite which frees the pro-peptide domain from the catalytic site and generates an active, 72 kDa MMP-2. Since hypertension is significant related to oxidative stress, and approximately half of newly formed MMP-2 is held inside the cell, increased peroxynitrite production may lead to the intracellular activation of MMP-2. MMP inhibitors may be a significant new opportunity to be used as adjuvants to treat hypertension as they substantially decrease maladaptive cardiovascular remodeling and then prevent the development of many other associated diseases. Antioxidants and antihypertensive drugs also contribute to decrease MMP activity and hypertrophic remodeling in hypertension. New pharmacological tools are needed to specifically decrease intracellular MMP-2 activity and thus help reduce cell migration and hypertrophy in hypertension. Keywords: hypertension, matrix metalloproteinases, cardiovascular remodeling, matrix metalloproteinase inhibitors, antioxidants
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".