Differential Effects of Doxycycline, a Broad-Spectrum Matrix Metalloproteinase Inhibitor, on Angiotensin II–Induced Atherosclerosis and Abdominal Aortic Aneurysms
Bibliographic record
Abstract
OBJECTIVE: Angiotensin II (AngII) infusion into hyperlipidemic mice leads to the rapid formation of atherosclerotic lesions and abdominal aortic aneurysms (AAAs). To define the role of matrix metalloproteinases (MMPs) in the development of these vascular pathologies, we administered the broad-spectrum MMP inhibitor doxycycline to saline- and AngII-infused LDL receptor-/- mice. METHODS AND RESULTS: Mice were placed on a high-fat diet for 1 week before infusion with either saline or AngII (1000 ng x kg(-1) x min(-1)) via osmotic pumps for 28 days. Doxycycline (30 mg x kg(-1) x d(-1)) was administered in the drinking water to both saline- and AngII-infused mice. Administration of doxycycline did not significantly influence systolic blood pressure, serum cholesterol concentrations, or lipoprotein-cholesterol distribution. Doxycycline had no effect on the extent of atherosclerosis in saline- or AngII-infused mice. In contrast, doxycycline markedly reduced the incidence of AAA formation (86% vs 35%, AngII vs AngII+doxycycline, respectively; P<0.05), in addition to reducing aneurysm severity. CONCLUSIONS: These data do not imply a role for MMPs in AngII-induced atherosclerosis but provide evidence consistent with a role in AngII-induced AAA formation.
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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) | 0.001 | 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 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".