Abstract 19809: Interferon Regulatory Factor 2 Binding Protein 2 Inhibits Macrophage Inflammation and Reduces Susceptibility to Atherosclerosis in Mice and Humans
Bibliographic record
Abstract
Introduction: Genetic variants near the gene encoding the transcription cofactor Interferon Regulatory Factor 2 Binding Protein 2 (IRF2BP2) have been tied to ischemic heart disease progression and elevated serum cholesterol. Expression of IRF2BP2 is suppressed in inflammatory macrophages, but the significance of this down-regulation was not known. Hypothesis: This study sought to determine the function of IRF2BP2 in macrophages and its effect on atherosclerosis in mice and humans. Methods and Results: We generated mice that delete IRF2BP2 in macrophages (LysMCre/IRF2BP2flox). IRF2BP2-deficient macrophages increased atherosclerosis in irradiated LDL-receptor null recipient mice and in ApoE null mice. Atherosclerosis was associated with a skewed inflammatory macrophage polarization and increased foam cell formation. Microarray analysis revealed and promoter studies confirmed that the anti-inflammatory transcription factor KLF2 is a target of IRF2BP2, indicating an important role for IRF2BP2 in macrophage polarization. A deletion polymorphism (rs3045215) in the 3’ untranslated sequence of human IRF2BP2 mRNA was examined for its effect on protein expression and on the susceptibility to coronary artery disease (CAD) risk in a cohort of 1,066 angiographic cases and 1,011 controls. Homozygous carriers of this deletion had lower IRF2BP2 (and its target KLF2) protein levels in peripheral blood mononuclear cells and a higher risk of CAD (recessive model, odds ratio (95%CI) = 1.560 (1.179-2.065), p=1.73E-03). The effect of this deletion to suppress protein expression was confirmed with luciferase reporter studies. Haplotype phasing identified two surrogate SNPs in modest LD (rs1887917, r2= 0.755 and rs632180, r2=0.614) that also associated with CAD in a recessive model. These SNPs are being tested for association with CAD in a large international consortium. Conclusion: Ablation of IRF2BP2 in macrophages worsens atherosclerosis in mice and a deletion variant that lowers IRF2BP2 expression predisposes to CAD in humans.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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) | 0.006 | 0.002 |
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".