Abstract 16544: Small Rna-sequencing Analysis of Circulating Proinflammatory Microrna Following Murine Myocardial Ischemia/reperfusion Injury
Bibliographic record
Abstract
Introduction: Transient myocardial ischemic/reperfusion injury (I/R) leads to cellular RNA release into extracellular (ex) space. Ex-RNAs and certain uridine-rich miRNAs activate innate immune response via TLR7-MyD88 pathway. Systemic administration of RNase reduces myocardial inflammation and infarct size after I/R, suggesting a pivotal role of ex-RNA in I/R injury. However, the nature of plasma RNAs and their biological functions in inflammation are not well understood. Hypothesis: Multiple plasma miRNAs are elevated in response to myocardial I/R injury and some are proinflammatory. Methods: Myocardial I/R injury was created in C57BL/6 mice by thoracotomy and 45 min of left anterior descending (LAD) ligation followed by 4 h of reperfusion. Sham mice underwent same procedure without LAD ligation. Plasma RNA was extracted using Trizol LS with Cel-miR-39 as spiked-in and quantified by RNA Quant-it kits. The plasma RNA was used to create cDNA libraries for small RNA sequencing (Norgen, Canada). Three abundant miRNAs that were differentially expressed between sham and I/R groups were tested for their proinflammatory effect. Results: Myocardial I/R led to a marked increase in plasma troponin (392.1±324.6 vs. 17.9±9.9ng/ml, P<0.05) and RNA levels (163±129 vs. 81±40 ng/ml) as compared with sham mice ( Fig. A ). Plasma RNA-Seq revealed miRNA was the predominate biotype constituting of 85.7% and 79.2% of plasma RNA in sham and I/R mice, respectively ( Fig. B ). We validated three miRNA expressions using qRT-PCR and found miR191-5p, miR125a-5p, and miR125b-5p were substantially increased ( Fig. C ). When incubated with macrophage cultures, miR125a-5p and miR-125b-5p, but not miR-191-5p, induced a dose-dependent response in CXCL-2 and IL-6 productions ( Fig. D ). Conclusions: Myocardial I/R injury results in an increase in multiple miRNAs in plasma. miR125a-5p and miR125b-5p, but not miR-191-5p, are pro-inflammatory in macrophages.
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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) | 0.000 | 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) | 0.003 | 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".