Abstract 545: Generation of Oxidized Phosphatidylcholines During Hypoxia-Reoxygenation Triggers Cell Death of Postnatal Cardiac Myocytes
Bibliographic record
Abstract
Reperfusion of ischemic heart tissue leads to a rapid burst of reactive oxygen species which initiates a cascade of events that cumulate in cell death. The most susceptible biomolecules to oxidative injury are membrane associated phospholipids. Oxidized phospholipids including oxidized phosphatidylcholines (OxPC), have shown to be potent activators of the intrinsic apoptotic signaling cascade. We hypothesize that the production of OxPC within hypoxic myocytes mediates damage from hypoxia-reoxygenation (H-R) by triggering inappropriate cardiac myocytes death. Hence, we determined whether, bioactive OxPC are produced in cardiomyocytes during H-R, and whether OxPC species induces apoptotic response resulting in cell death of cardiomyocytes. Post-natal rat cardiomyocytes were isolated from 2 d old rat pups and submitted to primary culture in serum-free medium. Cardiac myocytes were subjected to hypoxia (H) for 1 hour in a specialized gas-tight chamber under continuous nitrogen atmosphere followed by 1 hour reoxygenation (R). Lipidomic analysis of cardiac myocytes following H-R was determined by high performance liquid chromatography linked to tandem mass spectrometry was used to quantitate 82 distinct OxPC species from cell lipid extracts. Cell viability of cardiomyocytes was assessed in the absence and presence of known OxPC molecules (POVPC, PONPC, PGPC, PAzPC) and control non-oxidized PSPC. Lipidomic analysis of OxPC species showed increased generation of fragmented OxPC after H-R (10.20±0.67μg/mL vs1.95±0.24μg/mL, p<0.005) when compared to control cells. Cells exposed to POVPC and PONPC showed marked dose dependent increase in cell death compared to equal molar concentration of PSPC. There was also marked increase in mitochondrial permeability upon exposure to fragmented OxPC molecules. To our knowledge this is the first demonstration that OxPC are generated within post-natal cardiomyocytes during H-R and potent inducers of cell death of cardiac myocyte during H-R. Interventions designed to modulate the synthesis of cytotoxic OxPC during H-R may prove beneficial in suppressing aberrant cardiac myocyte cell death and loss of ventricular function in patients with ischemic heart disease or following myocardial infarction.
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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 | 0.001 |
| 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".