Abstract 15505: Cardiac-Specific Jarid2 Deficiency, Results in Improved Survival and Myocardial Function Following Experimental Sepsis
Bibliographic record
Abstract
Introduction: Myocardial depression and associated hemodynamic collapse are among the major causes of death in severe sepsis. Management of severe sepsis is largely supportive. Hypothesis: Emerging evidence suggests that the transcriptional repressor Jarid2 may play a regulatory role in sepsis; however, the functional role of Jarid2 in sepsis-induced myocardial dysfunction remains uninvestigated. Methods: Using both in in vivo (murine model of cecum ligation and puncture (CLP) in 12-week-old C57-wild type (WT) and cardiac specific Jarid2(knock-out, KO)) and in vitro (lipopolysaccharide, LPS) treatment of cultured murine cardiac myocytes) approaches we determined whether Jarid2 is a putative novel target for sepsis. Results: In response to CLP for 48hrs, WT displayed >60% mortality, survivors developed bacterial peritonitis, a marked inflammatory response (3-5-fold increases in serum and left ventricular (LV) interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha), myocardial dysfunction (20-35% decreases in dp/dt and echo-derived % ejection fraction (EF) and % fractional shortening (FS)), and a 40-50% decrease in LV Jarid2mRNA and protein compared to WT-sham. Jarid2KO mice showed resistance to CLP-induced bacterial peritonitis resulting in improved cardiac function (10-15% decrease in %EF and %FS), and survival (>90%) despite an exacerbated (10-15-fold increase in LV) inflammatory response compared to WT mice. In adult cultured cardiac myocytes derived from WT and Jarid2KO mice, treatment with the endotoxin LPS (1 microgram/mL) for 24 hrs, resulted in an 8-10-fold and 20-35-fold increase respectively, in the inflammatory cytokines TNF-alpha, IL-1beta and IL-6. Conclusions: These findings reveal that the loss of Jarid2 enhances bacterial clearance and despite an enhanced inflammatory response, resulted in improved myocardial function and survival following CLP-induced sepsis. As such, Jarid2 may be a novel therapeutic target in the treatment of sepsis-induced myocardial dysfunction.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".