High Levels of Plasma and Plaque IsoDGR-Modified Fibronectin are Associated with Rupture Prone Plaque Characteristics in Carotid Endarterectomy Patients
Bibliographic record
Abstract
OBJECTIVE: Macrophage influx is an important feature of human plaque destabilisation. Studies in mice suggest a role of the isoD(Asp)G(Gly)R(Arg) three amino acid motif in fibronectin (isoDGR-modified fibronectin) in macrophage influx. The association between isoDGR fibronectin in human plasma and plaque with plaque macrophage influx and vulnerable plaque characteristics has not been investigated in large human cohorts. METHODS: Levels of isoDGR fibronectin were measured in individual plasma and plaques from carotid endarterectomy (CEA) patients from the Athero-Express biobank and associated with macrophage content and other vulnerable plaque characteristics in the carotid plaque of the same patient. Levels of isoDGR fibronectin were measured using an enzyme linked immunosorbent assay. Carotid plaque characteristics were visualised with immunohistochemistry staining and scored semi-quantitatively. Baseline characteristics were analysed with Pearson's chi squared test and Mann-Whitney U test when applicable. Uni- and multivariable logistic regression analyses were used to identify associations with adverse plaque characteristics. RESULTS: Plasma isoDGR fibronectin was measured in 730 CEA patients (12.3% asymptomatic). Patients with moderate or heavy plaque macrophage staining had higher levels of isoDGR fibronectin than patients with no or minor macrophage staining (multivariable odds ratio [OR] 1.40, 95% confidence interval [CI] 1.04 - 1.90; p = .028). Of the 730 CEA patients, 348 had plaque samples available for isoDGR fibronectin measurements. In the multivariable analysis, higher plaque levels of isoDGR fibronectin were associated with moderate or high plaque macrophage staining (OR 1.22, 95% CI 1.00 - 1.56; p = .049), > 40% plaque area of fat (OR 1.44, 95% CI 1.14 - 1.86; p = .004), and intraplaque haemorrhage (OR 1.38, 95% 1.12 - 1.72; p = .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 destabilisation and blocking isoDGR modifications as a potential treatment modality.
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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 | 0.001 | 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".