Abstract 608: Valsartan Reverses Post-Translational Modifications of ATP Synthase D-Chain During Prolonged Post-Ischemic Reperfusion
Bibliographic record
Abstract
We hypothesized that reperfused myocardial infarction (RMI) induces post-translational modifications (PTMs) of the metabolic enzyme mitochondrial ATP synthase D-chain (ATP/D) which are reversed by the angiotensin II type 1 receptor (AT 1 R) blocker valsartan. We applied a pharmaco-proteomics approach to detect regional differences in PTMs of ATP/D in ischemic (IZ) and non-ischemic (NIZ) zones of hearts subjected to in vivo RMI (90 min left anterior descending coronary occlusion; 120 min reperfusion) in dogs randomized to placebo or valsartan. We measured hemodynamics and left ventricular (LV) function (2D-Echocardiogram/ Doppler) and identified/analyzed ATP/D using 2D electrophoresis, PD Quest, and in-gel trypsin digestion of protein spots (Fig. A ) followed by mass spectrometry, and FindMod tool for finding potential PTMs. Compared to sham, RMI induced ischemic injury and systolic and diastolic dysfunction in the placebo group and these were attenuated by valsartan. Compared to the NIZ, RMI increased ATP/D in the IZ (nearly 2-fold) and this was normalized by valsartan (Fig. B ). Importantly, RMI increased hydroxylation of ATP/D, S-nitrosylation of cysteine-100, nitration of tyrosine-80 and -225, and hydroxylation of lysine-182 followed by its myristoylation (Fig. C ). Valsartan reduced ATP/D hydroxylation, abolished the PTMs including lysine myristoylation in the IZ, and additionally triggered phosphorylation of serine-76 in both the IZ and NIZ. Valsartan-induced cardioprotection is associated with reversal of PTMs of ATP/D during RMI. This new pleiotropic effect of AT 1 R blockade suggests that PTMs may represent a novel therapeutic target after RMI.
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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".