Dilating the degradome: matrix metalloproteinase 2 (MMP-2) cuts to the heart of the matter
Bibliographic record
Abstract
With recent work revealing that MMPs (matrix metalloproteinases) cleave an increasingly large degradome of bioactive and signalling molecules, the dogma that MMPs are extracellular-matrix-remodelling proteases is under challenge. In this issue of the Biochemical Journal, Martínez et al. have reported that AM (adrenomedullin), a potent vasodilator predominantly expressed by blood vessel endothelial and smooth muscle cells, and microvasculature-rich tissues, is another new bioactive substrate for MMPs in vivo. Cleavage by MMP-2, but not MMP-9, generates a series of peptides; two of which retain receptor agonist and vasodilator activity, three are inactive and, excitingly, AM(11-22), a small product containing a canonical disulphide loop, is a vasoconstrictor. In view of the robust vasodilatory and other cardiac protective activities of AM in inhibiting myocardial fibrosis this represents a potent new systemic role for MMP-2 in the cardiovasculature. Hence, the paper by Martínez et al. directly implicates MMP activity in the development of hypertension and paradoxically in stimulating myocardial fibrosis, therefore pointing to exciting new possibilities for utilizing MMP-2-specific inhibitors as a new mode to treat blood pressure and heart disease.
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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 | 0.001 |
| 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 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.004 |
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".