Abstract 4369077: Postoperative Inflammation Promotes HDL Dysfunction, Disrupting Reverse Cholesterol Transport and Driving Rapid Atherosclerotic Plaque Destabilization
Bibliographic record
Abstract
Background: Myocardial Injury after Noncardiac Surgery (MINS) affects ∼1 in 6 patients undergoing major noncardiac procedures. A subset of MINS cases is linked to atherosclerotic plaque disruption, but the mechanisms driving this postoperative instability remain poorly defined. Reverse Cholesterol Transport (RCT), the removal of peripheral cholesterol by HDL and apoA-I, is critical for limiting plaque progression. Surgical inflammation is known to impair HDL function, but its impact on RCT and plaque stability is poorly understood. Hypothesis: Postoperative inflammatory remodeling of the HDL proteome impairs RCT, promoting cholesterol accumulation and necrotic core expansion in atherosclerotic plaques. Results: ApoE -/- mice on a Western diet underwent exploratory laparotomy or anesthesia only (control). LC-MS/MS of HPLC-isolated HDL revealed extensive postoperative inflammatory remodeling, marked by elevated serum amyloid A (SAA) and reduced apoA-I, impairing multiple RCT-related pathways as identified by Gene Ontology analysis. In vitro, macrophage (MΦ) cholesterol efflux to postoperative plasma and HDL was substantially reduced, while vascular smooth muscle cell (VSMC) efflux showed modest reductions. Using a novel dual-label, dual-cell-type in vivo RCT assay—subcutaneously injecting 3 H-cholesterol-labeled MΦs and 14 C-cholesterol-labeled VSMCs—MΦ RCT was significantly impaired for >48h post-op, whereas VSMC RCT was largely preserved. In human noncardiac surgery patients (n=21), in vitro MΦ cholesterol efflux to postoperative plasma was similarly impaired. In plaques, lipid accumulation (BODIPY) and perilipin-2 (PLIN2) expression increased in both MΦs and VSMCs at 24h after surgery. Apoptotic (cleaved caspase-3 + ) cells were enriched postoperatively, predominantly among PLIN2 high populations. Neutrophil extracellular traps (H3Cit + MPO + ) and inflammatory MΦs (TREM1 + ) were also elevated. By 72h and 15d postop, plaques exhibited reduced cellularity, fewer lipid-rich cells, and increased necrotic core area, suggesting acute lipid loading contributed to cell death and destabilization. Notably, rApoA-I treatment partially restored RCT and reduced plaque lipid accumulation. Conclusion: Postoperative inflammation disrupts RCT, driving lipid accumulation, cell death, and plaque destabilization. These findings reveal remarkably rapid, inflammation-driven changes in plaque lipid handling after surgery and suggest potential for targeted postoperative interventions.
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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 | 0.000 | 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 | 0.000 |
| 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".