High levels of IsoDGR-modified fibronectin are associated with higher levels of macrophages and other rupture-prone plaque characteristics in patients undergoing carotid endarterectomy
Bibliographic record
Abstract
Objective: Deamidation of the NGR (Asn-Gly-Arg) motif to the isoDGR (isoAsp-Gly-Arg) motif in fibronectin (IsoDGR-fibronectin) enhances in vitro monocyte and endothelial cell activation. Blocking isoDGR reduces macrophage influx in murine tissues. Although macrophage influx is an important feature of human plaque destabilization, the role for plasma and plaque isoDGR-fibronectin in macrophage influx in the atherosclerotic plaque and thereby increasing plaque vulnerability has not been investigated in large human cohorts. Design: IsoDGR-fibronectin levels in plasma and plaques were measured in carotid endarterectomy (CEA) patients from the Athero Express biobank cohort and associated with macrophage and other vulnerable plaque characteristics in the carotid plaque of the same patient. Methods: Levels of isoDGR-fibronectin were measured using an ELISA. Carotid plaque characteristics were visualized with immunohistochemistry staining and scored semi-quantitatively. Baseline characteristics were analysed with Pearson`s Chi-squared test and Mann-Whitney U-test when applicable. Univariate and multivariate logistics regression analyses were used to identify associations with adverse plaque characteristics. Results: Plasma isoDGR-fibronectin was measured in 730 CEA patients. Patients with moderate/heavy plaque macrophage staining had higher levels of isoDGR-fibronectin than patients with no/minor macrophage staining (multivariate OR 1.40 (95%CI 1.04-1.90, p=0.028)). Of the 730 CEA patients, 348 had plaque samples available for isoDGR-fibronectin measurements. In the multivariate analysis, higher plaque levels of isoDGR-fibronectin were associated with moderate/high plaque macrophage staining (OR 1.22 (95%CI 1.00-1.56, p=0.049)), >40% fat in plaque (OR 1.1.44 (95% CI 1.14-1.86, p=0.004)) and intraplaque haemorrhage (OR 1.38 (95% 1.12-1.72, p=0.003)). Conclusion: In this large human cohort study high plasma and plaque levels of isoDGR-fibronectin were associated with more plaque macrophages and other adverse plaque characteristics. This suggests the involvement of isoDGR-fibronectin in human plaque destabilization that may lead to new potential treatment modalities.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.002 | 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".