Abstract 250: Differential Role of Autophagy in Idiopathic versus Ischemic Heart Failure in Humans
Bibliographic record
Abstract
Background: Autophagy is an evolutionary conserved process that plays a key role in a variety of physiological and pathological processes. Despite its beneficial role, excessive/insufficient autophagic activity is known to contribute to the pathogenesis of cardiovascular disorders, including ischemia/reperfusion injury and heart failure. However, the differential role of autophagy in idiopathic versus ischemic heart failure remains unknown. Methods: To investigate the role of autophagy and associated apoptosis in idiopathic versus ischemic heart failure, we obtained LV myocardium biopsies from healthy controls (via 3 commercial sources), and from 10 patients with idiopathic and ischemic end-stage heart failure before the insertion of a left ventricular assist devise. The expression of inducers/markers of autophagy (mTOR, phospho-mTOR, LC3-I/II, p62, Beclin-1, autophagy-related genes ATG4B/ATG5) and apoptosis (Bcl-2 and caspase-3) were assessed at the transcript and protein level using quantitative RT-PCR and Western blotting. Results: Autophagy was activated in both idiopathic and ischemic heart failure in comparison to control, as confirmed by a significant reduction in mTOR expression/activation and a 3.4-fold and 2.2-fold increase in LC3 II/I ratio, respectively. An increase in apoptosis, marked by increased caspase3 and Bcl2 expression, was also observed in both groups in comparison to control. Interestingly, autophagy activity—marked by decreased mTOR expression/activation, increased ATG4B, ATG5, and Beclin-1—was significantly higher in idiopathic heart failure, when compared to ischemic heart failure. While we observed increased autophagic activity in idiopathic heart failure, p62 expression was also significantly increased in this group (2.8-fold increase; p<0.05), demonstrating an impairment of autophagic flux in idiopathic versus ischemic heart failure. Conclusions: For the first time, we provide a direct comparision of autophagy and apoptosis in idiopathic versus ischemic heart failure. Our data, demonstrating an excessive yet insufficient autophagic activity in idiopathic heart failure, suggests a differential role of autophagy apoptosis in idiopathic versus ischemia-related heart failure.
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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 | 0.000 |
| 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) | 0.001 | 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".