Abstract 16815: Cholesterol Efflux Capcity in Genetic Forms of HDL Deficiency
Bibliographic record
Abstract
Objective: High-density lipoprotein cholesterol (HDL-C) deficiency is the most frequent lipoprotein abnormality in patients with premature coronary artery disease. In order to determine the functionality of HDL particles in genetically defined HDL deficiency (<5th percentile), we employed a cell-based assay to examine ABCA1-dependent cholesterol efflux capacity in apoB-depleted plasma isolated from 19 probands of French Canadian descent. First degree relatives with normal HDL levels served as controls. Methods and Results: We determined the ability of apoB-depleted plasma to promote cholesterol efflux from [ 3 H] cholesterol-labeled, cAMP-stimulated J774 macrophages. Cases consisted of 16 ABCA1 heterozygotes, and three APOA1 E136X heterozygotes. We obtained evidence that ApoB-depleted plasma isolated from subjects with genetic forms of HDL deficiency had significantly reduced levels of ABCA1-mediated cholesterol efflux as compared to sibling controls (72.33 %). Conversely, when normalized to apoA-I levels, the efflux capacity of apoB-depleted plasma from subjects was attenuated as compared to sibling controls. Linear regression was used to determine which biochemical measurement (apoA-I concentration, HDL-C level and HDL subfractions quantified by 2DPAGGE) best explained the cholesterol efflux results. A strong, positive correlation was found between cholesterol efflux measurements and apoA-I levels, HDL-C levels, alpha-2 HDL levels, and alpha-3 HDL levels (all p< 0.05). However, HDL-C levels only explained approximately 27% of the variability in cellular cholesterol efflux, suggesting that efflux capacity may help better understand HDL functionality. Conclusion: While HDL obtained from subjects with ABCA1 or APOA1 gene defects had decreased cellular cholesterol efflux compared with sibling controls, this difference was markedly attenuated when corrected for apoA-I mass, suggesting that such particles remain functional in cholesterol efflux through ABCA1.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.003 | 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 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".