Matrix metalloproteinase‐2 co‐localizes with titin in cardiac myocytes and contributes to its proteolysis in ischemia‐reperfusion injury
Bibliographic record
Abstract
Titin, the largest known protein in mammalian cells, plays a central role as a molecular spring of the cardiomyocyte and thus is an important determinant of cardiac function. Although loss of titin in ischemic hearts has been reported, the mechanism of this is unclear. Matrix metalloproteinase‐2 (MMP‐2) is a protease ubiquitously expressed in cardiomyocytes. We have shown that MMP‐2 is localized to the cardiac sarcomere and proteolyzes specific myofilament proteins in ischemia‐reperfusion (I‐R) injury. Hypothesis Titin is an intracellular substrate for MMP‐2 and its degradation during I‐R contributes to cardiac dysfunction. Results Immunohistochemistry showed the clear co‐localization of MMP‐2 and titin using an antibody to the Z disc region. In vitro incubation of purified titin with MMP‐2 led to titin degradation which was prevented by inhibiting MMP‐2. Isolated working rat hearts were subjected to I‐R injury (25 min global, no‐flow ischemia followed by 60 min aerobic reperfusion) with or without ONO4817 (MMP‐2/9 inhibitor). Titin in heart samples was analyzed by gel electrophoresis (1% agarose‐SDS) and immunohistochemistry. I‐R caused a loss of titin in the heart. ONO4817 prevented I‐R‐induced titin degradation and improved the recovery of mechanical function. Conclusion MMP‐2 localizes to titin at the Z disc region of the cardiac sarcomere and contributes to titin degradation in I/R injury.
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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) | 0.001 | 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".