MK2-deficient mice are bradycardic and display delayed hypertrophic remodelling in response to a chronic increase in afterload
Bibliographic record
Abstract
Abstract MAP kinase-activated protein kinase-2 (MK2) is protein serine/threonine kinase activated by p38α/β. Herein we examined the cardiac phenotype of pan MK2-null (MK2 −/− ) mice. 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, ageing 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 (mPTP) opening. Finally, the pressure overload-induced increase in heart weight/tibia length and decrease in systolic function were attenuated in MK2 −/− mice two weeks, but not eight weeks, after constriction of the transverse aorta. Collectively, these results implicate MK2 in (i) autonomic regulation of heart rate, (ii) cardiac mitochondrial function, and (iii) the early stages of myocardial remodeling in response to chronic pressure overload. Key points summary The cardiac characterization of pan MK2-null mice showed: altered autonomic regulation of heart rate increased expression of key metabolic genes decreased Ca 2+ -sensitivity for MPTP opening delayed hypertrophic remodeling in response to increased afterload
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".