Abstract 101: Dipeptidylpeptidase-iv Inhibition Using MK626 Attenuates BAPB/AT2 Induced Murine Aneurysm
Bibliographic record
Abstract
The dearth of effective treatments to diminish aneurysm progression is a recognized clinical challenge. Modulation of the glucagon-like peptide-1 (GLP-1) pathway is a recent addition to anti-diabetic management regimes, and has pleiotropic effects to inhibit arterial wall macrophage infiltration, a key pathological event in aneurysmal disease. We therefore hypothesized that inhibition of endogenous breakdown of GLP-1, using the dipeptidylpeptidase-IV inhibitor MK626, would attenuate BAPN/AT2 induced murine aneurysm. Eight-week-old C57/Bl6 mice received two weeks of oral beta-aminopropriononitrile (BAPN) and four weeks of angiotensin-2 (AT2) via mini-osmotic pump. MK626 3mg/kg in methylcellulose vehicle was administered daily and compared to control methylcellulose vehicle. At four weeks, whole aortas were dissected and photomicrographed. Cross sections of aorta were stained using H&E and EVG. Compared to wild-type, BAPN/AT2 caused dilatation of the aorta from the ascending to the suprarenal segment (p<0.002) with infrarenal sparing (p=0.77). Focal aneurysmal dilatation reproducibly occurred in the suprarenal aorta (wild-type diameter 0.93±0.03mm, n=8; BAPN/AT2 diameter 2.26±0.12, n=8; p<0.0001). Treatment with MK626 attenuated dilatation of the descending aorta compared to controls (BAPN/AT2 control 1.26±0.05mm, n=8; MK626 1.07±0.05mm, n=10; p=0.03). The focal suprarenal aneurysmal dilatation was significantly reduced by treatment with MK626 (BAPN AT2 control 2.26±0.34mm, n=8; MK626 1.66±0.32mm, n=10; p=0.0001). BAPN/AT2 induced aortic aneurysm was associated with excess matrix deposition, increased medial thickness, and elastic fibre fragmentation. Modulation of the GLP pathway using the dipeptidylpeptidase-IV inhibitor MK626 attenuates aneurysm in a BAPN/AT2 induced murine model.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".