Monomeric C-Reactive Protein Decreases Acetylated LDL Uptake in Human Endothelial Cells
Bibliographic record
Abstract
BACKGROUND: C-reactive protein (CRP) is a risk marker for cardiovascular disease and has been implicated in atherogenesis. In atherosclerotic plaques, it colocalizes with oxidized LDL (oxLDL) and promotes oxLDL uptake by macrophages, suggesting an important cross-talk between CRP and lipid processing. A growing body of evidence indicates the existence of distinct configurations of human CRP, native pentameric (nCRP) and structurally modified monomeric (mCRP), that elicit opposing bioactivities in vitro and in vivo. Here, we tested the impact of mCRP and nCRP on the uptake of acetylated LDL (acLDL), which is internalized by receptors similar to those of oxLDL in human endothelial cells. METHODS: We cultured human umbilical vein endothelial cells (HUVECs) for 8 h with mCRP or nCRP (10-100 mg/L) and measured the uptake of acLDL (10-100 mg/L) over a 20-h period by FACS analysis. To assess the receptors involved, we used function-blocking antibodies against Fc gamma receptor CD16 (FcgammaRIII) and CD32 (FcgammaRII), and RT-PCR analysis of CD16, CD32, and the receptor for oxidized LDL (LOX-1). Uptake of acLDL and CRP isoforms was visualized by immunofluorescence. RESULTS: Culture of HUVECs with mCRP, but not nCRP, decreased uptake of acLDL, which was not prevented by anti-CD16 or anti-CD32 antibodies. LOX-1, CD16, and CD32 were undetectable by RT-PCR. Immunofluorescence showed decreased cytoplasmic acLDL staining in human umbilical vein endothelial cells (HUVECs) treated with mCRP, but not with nCRP. CONCLUSIONS: Monomeric CRP, but not nCRP, decreased acLDL uptake in human endothelial cells independent of CD16, CD32, or LOX-1. Our data support a protective role of mCRP in cardiovascular disease.
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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) | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".