HDLs and the pathogenesis of atherosclerosis
Bibliographic record
Abstract
PURPOSE OF REVIEW: Plasma levels of HDL cholesterol are a biomarker of cardiovascular health but not a therapeutic target, as demonstrated by the failure of pharmacological modulation of HDL cholesterol to prevent or treat atherosclerotic cardiovascular disease. In health, HDL particles exert pleiotropic effects against atherosclerosis, including cholesterol removal from foam cells, vasodilatory effects through vascular endothelial cell nitric oxide production, decreased vascular inflammation and oxidative damage, endothelial cell proliferation and antiapoptotic effects. RECENT FINDINGS: These functional effects of HDL are independent of the cholesterol mass and are related to the proteome and lipidome. In disease states and with the ageing process, HDL components are extensively modified and may no longer play a beneficial role but are retained in the atheroma and contribute to atherosclerosis. We have recently shown that desmocollin 1 (DSC1) acts as an apolipoprotein (apo) A-I binding protein that is highly expressed in atherosclerotic plaques and inhibits atheroprotective HDL functions by retaining apoA-I. The apoA-I retention hypothesis proposes that macrophages express DSC1 in a maladaptive process that renders apoA-I inactive and contributes to atherosclerosis. SUMMARY: HDL loses their beneficial properties in ageing and disease states. Novel pathways may present new therapeutic avenues to restore their biological functions.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".