Abstract P302: CaMKII Is Not Critical for Ischemia/Reperfusion Injury
Bibliographic record
Abstract
Objectives: The role of the Calcium/calmodulin-dependent protein kinase II (CaMKII) in Ischemia/Reperfusion of the heart (I/R) has not completely been clarified yet - partly due to lacking evidence from animal studies with specific gene knockout (KO) strategies. Moreover, the contribution of the nuclear and cytosolic CaMKIIδ splice variants δB and δC to I/R-induced myocardial damage have been controversially discussed. To investigate the role of CaMKII in myocardial I/R we used several KO mice with genetic deletion of the two major isoforms expressed in the heart, CaMKIIδ and CaMKIIγ, respectively. Both single and double KO models were examined. In addition, we developed a reliable approach to express CaMKII δB and δC splice variants in CaMKIIδ-null mice using adeno-associated-virus serotype 9 (AAV9) to investigate their specific roles in I/R. Methods and Results: A surgical in vivo I/R model was used following two protocols: 30 minutes ischemia with 48 hours of subsequent reperfusion (30/48) and 60 minutes ischemia followed by a 24 hour reperfusion period (60/24). Planimetric measurements of infarct size after staining with Evans Blue and Triphenyl tetrazolium chloride showed no significant difference between CaMKII KO and control groups (infarct-zone/area-at-risk ratio for 30/48-protocol: CaMKIIγ −/− vs. C57/Bl6: 0.49 ± 0.04 vs. 0.43 ± 0.05, p=0.43, n≥6; CaMKIIδ −/− vs. C57/Bl6: 0.42 ± 0.04 vs. 0.44 ± 0.04, p=0.69, n≥19; infarct-zone/area-atrisk ratio for 60/24-protocol: CaMKIIδ −/− vs. C57/Bl6: 0.52 ± 0.02 vs. 0.56 ± 0.03, p=0.33, n≥8; CaMKIIγ loxP/loxP δ loxP/loxP ; alphaMHC-Cre vs. CaMKIIγ loxP/loxP δ loxP/loxP : 0.52 ± 0.03 vs. 0.52 ± 0.04, p=0.86, n≥9). Consistently, no differences in high-sensitive serum troponin T levels 24 hours after onset of ischemia could be detected. Neither histologic TUNEL-staining nor Caspase3/7-acivity assays revealed any significant differences in apoptotic cell death processes. Importantly, specific expression of CaMKII δB or δC splice variants via AAV9 gene transfer - at approximate endogenous protein levels - in CaMKIIδ −/− mice had no effect on infarct size and necrotic or apoptotic markers. Conclusion: Our findings indicate that CaMKII is not critical for myocardial infarct size and apoptosis in response to I/R.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.022 | 0.006 |
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".