Does caveolin‐1 knockout affect matrix metalloproteinase‐2 activity and contractile function in the isolated working mouse heart?
Bibliographic record
Abstract
Matrix metalloproteinase‐2 (MMP‐2) proteolyzes troponin I (TnI), myosin light chain‐1 (MLC‐1) and α‐actinin within cardiomyocytes in hearts challenged with ischemia and reperfusion (I/R). MMP‐2 is also co‐localized with caveolin‐1 (Cav‐1) in cardiomyocytes. Cav‐1 inhibits MMP‐2 activity. Cav‐1 null (Cav‐1 −/− ) hearts have increased MMP‐2 activity. How this affects heart function in response to physiological and pharmacological challenges, and whether this has an impact on known MMP‐2 substrates, is unknown. Cav‐1 −/− or control (Cav‐1 +/+ ) hearts were isolated and perfused as working hearts. Hearts were perfused aerobically for 30 min followed by both physiological (preload varied between 7‐22.5 mmHg) and pharmacological (0.1‐100 nM isoproterenol) challenges. Cardiac function between the Cav‐1 −/− vs Cav‐1 +/+ hearts did not differ in either challenge. Gelatin zymography of heart homogenates showed no differences in MMP‐2 activity. Protein levels of MMP‐2, TnI, MLC‐1 and α‐actinin were similar between Cav‐1 +/+ and Cav‐1 −/− hearts. Hearts briefly perfused for 10 min showed more MMP‐2 activity compared with hearts perfused for 90 min. Prolonged perfusion and the oxidative stress inherent in the isolated working heart procedure may release MMP‐2 from the heart. MMP‐2 proteolysis of intracellular proteins may be dependent upon its activation in I/R. This work is supported by HSF, CIHR and AHFMR.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 |
| 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".