Increased Cell and Matrix Accumulation During Atherogenesis in Mice With Vessel Wall–Specific Deletion of Discoidin Domain Receptor 1
Bibliographic record
Abstract
RATIONALE: Discoidin domain receptor (DDR)1 is a collagen receptor expressed on both smooth muscle cells (SMCs) and macrophages, where it plays important roles regulating cell and matrix accumulation during atherogenesis. Systemic deletion of DDR1 resulted in attenuated plaque growth but accelerated matrix accumulation in LDLR-deficient mice. Deletion of DDR1 solely on bone marrow-derived cells resulted in decreased macrophage accumulation and plaque growth but no change in matrix accumulation. OBJECTIVE: These findings led us to hypothesize that accelerated matrix accumulation was attributable to the increased synthetic ability of Ddr1(-/-) resident vascular wall SMCs. METHODS AND RESULTS: We used bone marrow transplantation to generate chimeric mice and investigate the role of SMC DDR1 during atherogenesis. Mice with deficiency of DDR1 in vessel wall-derived cells (Ddr1(+/+-->-/-)) or control mice (Ddr1(+/+-->+/+)) were fed an atherogenic diet for 12 weeks. We observed a 3.8-fold increase in the size of aortic sinus plaques in Ddr1(+/+-->-/-) compared to Ddr1(+/+-->+/+) mice. This was attributed to pronounced accumulation of collagen, elastin, proteoglycans, and fibronectin and resulted in a thickened fibrous cap. The enhanced matrix accumulation decreased the proportion of plaque area occupied by cells but was associated with a shift in the cellular composition of the lesions toward increased numbers of vessel wall-derived SMCs compared to bone marrow-derived macrophages. In vitro studies confirmed that Ddr1(-/-) SMCs expressed more matrix, proliferated more, and migrated farther than Ddr1(+/+) SMCs. CONCLUSIONS: DDR1 expression on resident vessel wall SMCs limits proliferation, migration and matrix accumulation during atherogenesis.
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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 | 0.001 | 0.000 |
| 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) | 0.000 | 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".