Abstract P188: Suppression of MK2 Signaling Protects Against Pressure Overload-Induced Cardiac Dysfunction
Bibliographic record
Abstract
p38 mitogen-activated protein kinases (MAPKs) regulate a broad range of cellular activities but have been implicated in the pathogenesis of cardiovascular diseases. The mechanisms whereby p38 exerts divergent effects are unknown. Current p38 inhibitors both produce serious side effects and loose efficacy with chronic use. Hence, a better understanding of the downstream targets of p38, i.e. MAPK-activated protein kinases (MKs), is essential. We hypothesized that inhibition of MK2 activity (MK2-/-) during chronic pressure overload is cardioprotective. Twelve-week-old MK2-/- and littermate control (MK2+/+) mice were subjected to transverse aortic constriction (2 wks, n=8). MK2-/- mice showed a ∼20% reduced increase in heart weight-to-tibia length ratio (Fig A) despite similar increases in mean blood pressure and ANP expression. Compared to controls, banded MK2-/- hearts also showed preserved left ventricular: (i) fractional shortening, (ii) ejection fraction (preserved at 72.5 ± 2.2% after banding for MK2-/- but decreased from 67.9 ± 3.6% to 58.8 ± 3.4% in MK2+/+, p<0.05, Fig B), and (iii) diastolic function evidenced by the ratio of transmitral and myocardial early diastolic velocities (E/Em preserved after banding in MK2-/- but increased by 78.8 ± 11.1% in MK2+/+, p<0.01). MK2 deficiency did not reduce interstitial fibrosis. For equivalent respiration rates, mitochondria from MK2-/- hearts showed a significant decrease in Ca2+-sensitivity for mitochondrial permeability transition pore opening (p<0.05, Fig C). Overall, these results suggest that MK2 mediates part of the detrimental remodeling evoked by chronic pressure overload-induced activation of p38.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".