GATA2 Mediates Macrophage Proliferation During Atherosclerosis
Bibliographic record
Abstract
Atherosclerosis is fueled by the buildup of lipid-laden macrophages within the vascular intima. These macrophages are derived from monocytes that are recruited from the circulation into the developing lesion, where they proliferate and differentiate into macrophages, with proliferation producing most of the macrophages in the resulting lesions. However, the signals and transcriptional events driving the proliferation of atherosclerotic plaque macrophages remain poorly understood. Analysis of human plaque spanning a range of disease severity identified a subpopulation of macrophages that expressed the hematopoietic transcription factor GATA2. These GATA2-expressing macrophages had a transcriptional profile that was intermediary between monocytes and mature macrophages, and selectively upregulated genes associated with proliferation and apoptosis. The expression of GATA2 was concomitant with plaque macrophage proliferation at all stages of disease, with over 90% of proliferating macrophages expressing GATA2. GATA2 was upregulated in macrophages following exposure to oxLDL, with GATA2 expression being necessary and sufficient for the proliferation of these macrophages. In these cells, GATA2 mediates proliferation by upregulating expression of the proto-oncogene MYB, while simultaneously decreasing sensitivity to apoptosis induced by the unfolded protein response. Together, these data identify GATA2 as a transcription factor upregulated by atherogenic stimuli that functions as the primary mediator of macrophage proliferation in atherosclerotic plaque.
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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) | 0.000 | 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 | 0.000 | 0.001 |
| 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".