Abstract 630: Novel Chimeric Anti-proteoglycan Antibody Inhibits Arterial Retention of Proatherogenic Lipoproteins in a Rat Model of Insulin Resistance
Bibliographic record
Abstract
Background: The response-to-retention hypothesis for atherosclerosis describes subendothelial retention of apolipoprotein B-containing lipoproteins mediated by proteoglycans (PG). Further we know that diabetes is also associated with both increased circulating chylomicron remnants and remodeling of proatherogenic PGs. We have recently reported antiatherogenic properties of a novel chimeric monoclonal antibody (chP3R99) that recognizes PG sulfated molecules. Hypothesis: chP3R99 monoclonal antibody may interfere with the interaction of atherogenic lipoproteins with arterial sulfated PGs during insulin resistance. Methods and Results: chP3R99 antibody recognized sulfated glycosaminoglycans by ELISA showing a preferential binding to chondroitin sulfate. Also, chP3R99 blocked the interaction of proatherogenic lipoproteins with this glycosaminoglycan in vitro in a dose-dependent manner and its intravenous injection into healthy Sprague-Dawly rats (n=6, 1 mg/animal) inhibited LDL (4 mg/kg; intraperitoneally) aortic retention. To further assess this property in an insulin resistant condition, carotid arteries from control and JCR:LA-cp rats (n=4) were perfused ex vivo with apoB48 containing remnant lipoproteins (prepared via rabbit hepatectomy procedure), with or without Cy3-LDL (150 μg/mL) for 20 minutes. Confocal microscopy analysis revealed an increased arterial retention of both remnants (3.6 fold) and LDL (2.8 fold) in carotid vessels from insulin resistant rats relative to control. However, chP3R99 pre-perfusion resulted in decreased retention of remnants (-30%) and LDL (-60%) associated arterial cholesterol. Data suggests that the chP399 antibody may interfere with the arterial attachment of both remnants and LDL in vivo, but with differential efficacy. Conclusions: Relative to LDL, remnant lipoproteins had preferential accumulation in arterial vessels from insulin resistant rats ex vivo , which could then be inhibited by acute pre-exposure to the chP3R99 antibody. These in vivo data support the concept for an innovative approach to target the retention of proatherogenic lipoproteins in a pre-clinical setting.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".