Atheroregressive Potential of the Treatment with a Chimeric Monoclonal Antibody against Sulfated Glycosaminoglycans on Pre-existing Lesions in Apolipoprotein E-Deficient Mice
Bibliographic record
Abstract
The retention of lipoprotein particles in the intima, in particular to glycosaminoglycan side chains of proteoglycans, is a critical step in atherosclerosis initiation. Administration of chP3R99, a chimeric mouse/human monoclonal antibody inducing an anti-idiotypic network response against glycosaminoglycans was previously shown to prevent atherosclerotic lesion progression, yet its effect in the late-stage progression of lesions remains unknown. This study investigated the effect of chP3R99 at a late stage of disease development in apolipoprotein E-deficient mice and the vascular mechanisms involved. Male apolipoprotein E-deficient mice were fed a high fat high cholesterol diet from 4 to 19 weeks old, at which time mice were fed normal chow and 5 doses of chP3R99 (50 µg) or isotype-matched IgG (hR3) were administered subcutaneously weekly for the first 3 administrations, then at weeks 24 and 26 before sacrifice (week 28). Lesions progression was reduced by 88% in treated mice with no change in total plasma cholesterol levels, yet with increased sera reactivity to chP3R99 idiotype and heparin, suggesting the induction of an anti-idiotype antibody cascade against glycosaminoglycans, which was likely related with the atheroprotective effect. chP3R99 treatment initiated regression in a significant number of mice. Circulating levels of interleukin-6 were reduced along with a striking diminution of inflammatory cell accumulation in the vessel wall, and of VCAM-1 labeling in vivo. The ratio of IL-10/iNOS gene expression in aortas increased in chP3R99-treated mice. In conclusion, our results show that treatment with chP3R99 reduces vascular inflammatory burden and halts lesion progression with potential for regression in the late phase of the disease in atherosclerotic mice, and support the therapeutic intervention against glycosaminoglycans as a novel strategy to reverse atherosclerosis.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| 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 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".