Abstract 423: A Proatherosclerotic Environment Impacts the Function and Cellular Metabolism in Cardiac Mitochondria
Bibliographic record
Abstract
Apolipoprotein E (ApoE) is an important plasma lipoprotein, able to suppress atherosclerosis by promoting uptake of circulating cholesterol and lipid into the liver. A deficiency of ApoE (ApoE-/-) leads to fatty acid accumulation in the plasma and subsequent increase in reactive oxygen species generation. Mitochondria in cardiomyocytes, due to the nature of the tissue, rely primarily on oxidative pathways for energy production. How this altered lipid metabolism affects cardiac mitochondria, considering the heart relies predominantly on fats as its primary energy source, has yet to be elucidated. The aim of this study is to determine the influence of altered lipid metabolism, resulting from ApoE-/- on cardiac mitochondrial oxidative capacity. We assessed the hypothesis that cardiac mitochondria would be greatly influenced by a lack of ApoE, thus affecting substrate and energy metabolism, as well as oxygen consumption compared to controls. 2-month-old ApoE-/- mice (n=8) were compared to age-matched C57Bl/6 mice (n=8). All animals were fed a standard chow and had access to water ad libitum. Left ventricular cardiac tissue samples were permeabilized and exposed to a series of titrated substrates and inhibitors that acted on the mitochondrial respiratory complexes. High-resolution respirometry was used to determine mitochondrial oxidative capacity. Citrate synthase activity, immunoblotting and immunofluorescence were also performed. Statistical comparisons were drawn using a two-tailed Student’s t-test. For statistical evaluations, p < 0.05 was considered significant. The results revealed a decreased basal state 2 respiration, a decreased mitochondrial leak and a higher respiratory control ratio in the young ApoE-/- group compared to controls. Maximal state 3 respiration was similar in both groups. In conclusion, these findings indicate that ApoE deficiency seems to positively affect the coupling between oxidation and phosphorylation within cardiac mitochondria in young animals. Our results suggest that ApoE-/- actually benefits cardiac metabolism, at least in the early stages of accelerated lipid metabolism. More work is needed to determine if these observations remain as the animals age or whether these effects are time dependent.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".