Abstract 125: Intensive Statin Therapy Negatively Modulates AdipoR Activity in the Monocyte-macrophage Lineage <i>in vivo</i> and <i>in vitro</i>
Bibliographic record
Abstract
Introduction: Statins are widely used for primary and secondary prevention of cardiovascular disease and its complications through cholesterol lowering and anti-inflammatory effects. Adiponectin, an anti-inflammatory adipokine, acts via 2 receptors, AdipoR1 and AdipoR2, to exert protective effects on the vasculature. Recently, we demonstrated that AdipoR are highly expressed on macrophages and that decreased AdipoR2 activity is associated with atherosclerotic plaque instability. We aimed to investigate whether statins can modulate AdipoR activity in the monocyte-macrophage lineage. Methods: Blood monocytes were isolated from whole blood of patients (statin-naïve vs statin users) with severe carotid atherosclerosis by a Magnetic Cell-Sorting technique. AdipoR1 and AdipoR2 mRNA expression on circulating monocytes was determined using qRT-PCR. In vitro , THP-1 macrophages were treated for 24 or 72 hours with varying doses of atorvastatin or rosuvastatin (1μM, 10μM, 60μM) to determine the effect of statins on AdipoR activity (AMPK, PPAR-α) by qRT-PCR and Western Blot analyses. Macrophage cytokine secretion (IL-1β, IL-10, IL-6, TNF-α) was assessed by electrochemiluminescence. Results: AdipoR1 and AdipoR2 mRNA expression on circulating monocytes was significantly lower by 1.36- and 1.17-fold (P<0.05), respectively, in statin users (n=157) compared to statin-naïve patients (n=37). When analyzing by statin type and dose, only patients on high doses of atorvastatin (40-80 mg) or rosuvastatin (20-40 mg) had significantly lower AdipoR expression compared to statin-naïve patients (P<0.05). Statins effects on lowering AdipoR expression was only apparent in patients with unstable but not stable plaques. In vitro , higher doses and longer exposure of macrophages to atorvastatin or rosuvastatin resulted in a greater decrease in AdipoR mRNA expression and signalling through AMPK and PPAR-α, and greater secretion of pro-inflammatory cytokines, IL-1β, IL-6, and TNF-α. Conclusion: In our study, intensive statin therapy resulted in negative modulation of AdipoR expression and function. Despite their known protective properties, statins may also elicit severe adverse effects, which are often associated with long-term treatment and high doses.
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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) | 0.001 | 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) | 0.007 | 0.002 |
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".