Increased Cyclic Guanosine Monophosphate and Interleukin-1Beta Is Activated by Mitochondrial Dysfunction and Associated With Heart Failure in Atrial Fibrillation Patients
Bibliographic record
Abstract
Background: This study aimed to identify the association of cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator interferon genes (cGAS-STING) pathway with heart failure (HF) in atrial fibrillation (AF) patients. Methods: We prospectively enrolled 106 AF patients without evidence of HF. The serum levels of 2'3'-cyclic GMP-AMP (2'3'-cGAMP) and interleukin (IL)-1 were measured by enzyme-linked immunoassay (ELISA). To determine the underlying mechanism, we supplemented the complex I inhibitor rotenone and the specific cGAS inhibitor RU.521 in neonatal rat ventricular cardiomyocytes. Results: During 18-month follow-up, serum concentrations of 2'3'-cGAMP (baseline 51.82 11.34 pg/mL vs. follow-up 124.50 75.83 pg/mL, P paired t < 0.01) and IL-1 (baseline 436.07 165.82 vs. follow-up 632.48 119.25 ng/mL, P paired t < 0.01) were substantially upregulated in AF patients with HF as compared with those without HF. Furthermore, serum 2'3'-cGAMP and IL-1 levels at 18-month follow-up were independently associated with the occurrence of HF in AF patients. Inhibition of cGAS by RU.521 effectively reversed the upregulation of 2'3'-cGAMP and STING phosphorylation induced by mitochondrial dysfunction, accompanied with inhibition of nod-like receptor protein 3 (NLRP3) inflammasome, IL-1 and IL-18 secretion. Conclusions: Induction of mitochondrial dysfunction causes an upregulation of 2'3'-cGAMP and activation of NLRP3 inflammasome through cGAS-STING pathway in cardiomyocytes. Cardiol Res. 2024;15(2):108-116 doi: https://doi.org/10.14740/cr1613
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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 | 0.001 | 0.001 |
| 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 | 0.001 |
| 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".