MK2‐Deficient Mice Are Bradycardic and Display Delayed Hypertrophic Remodeling in Response to a Chronic Increase in Afterload
Bibliographic record
Abstract
Background Mitogen‐activated protein kinase–activated protein kinase‐2 (MK2) is a protein serine/threonine kinase activated by p38α/β. Herein, we examine the cardiac phenotype of pan MK2‐null (MK2 −/− ) mice. Methods and Results Survival curves for male MK2 +/+ and MK2 −/− mice did not differ (Mantel‐Cox test, P =0.580). At 12 weeks of age, MK2 −/− mice exhibited normal systolic function along with signs of possible early diastolic dysfunction; however, aging was not associated with an abnormal reduction in diastolic function. Both R‐R interval and P‐R segment durations were prolonged in MK2‐deficient mice. However, heart rates normalized when isolated hearts were perfused ex vivo in working mode. Ca 2+ transients evoked by field stimulation or caffeine were similar in ventricular myocytes from MK2 +/+ and MK2 −/− mice. MK2 −/− mice had lower body temperature and an age‐dependent reduction in body weight. mRNA levels of key metabolic genes, including Ppargc1a , Acadm , Lipe , and Ucp3, were increased in hearts from MK2 −/− mice. For equivalent respiration rates, mitochondria from MK2 −/− hearts showed a significant decrease in Ca 2+ sensitivity to mitochondrial permeability transition pore opening. Eight weeks of pressure overload increased left ventricular mass in MK2 +/+ and MK2 −/− mice; however, after 2 weeks the increase was significant in MK2 +/+ but not MK2 −/− mice. Finally, the pressure overload–induced decrease in systolic function was attenuated in MK2 −/− mice 2 weeks, but not 8 weeks, after constriction of the transverse aorta. Conclusions Collectively, these results implicate MK2 in (1) autonomic regulation of heart rate, (2) cardiac mitochondrial function, and (3) the early stages of myocardial remodeling in response to chronic pressure overload.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".