Apolipoprotein-A1 transports and regulates MMP2 in the blood
Bibliographic record
Abstract
Abstract Synthesized in the liver and intestines, apolipoprotein A1 (ApoA1) is the major protein component of high-density lipoprotein (HDL) particles and transports cholesterol from peripheral organs to the liver. This interorgan communication strategy may protect against atherogenesis by sequestering cholesterol from atherosclerotic lesions. Here, we found that ApoA1 has high affinity for the catalytic groove and fibronectin-like repeats of matrix metalloproteinase 2 (MMP2), the most abundant MMP in human blood. In healthy humans and ApoA1-expressing mice, we found that MMP2 is associated with ApoA1 in HDL. We confirmed the ApoA1/MMP2 interactions using five orthogonal interaction proteomics assays. Strikingly, we found that Apoa1 can allosterically increase the proteolytic activity of MMP2—an effect not observed in ApoA1-deficient plasma from ApoA1 KO mice. This finding was not predictable, as MMP2 was not previously known to be an allosteric enzyme. Using a high-confidence artificial intelligence (AlfaFold)-based structural model of the ApoA1/MMP2 complex, we explain how ApoA1 binds and allosterically regulates MMP2. We suggest that ApoA1 sequesters MMP2 in the blood circulation and redistributes it to ApoA1 target organs, such as the liver. This interorgan communication mechanism is independent of canonical reverse cholesterol transport by ApoA1/HDL and may prevent MMP2-mediated rupture of atherosclerotic plaques. Graphical Abstract
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.047 | 0.006 |
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".