Ovariectomy in aged versus young rats augments matrix metalloproteinase-mediated vasoconstriction in mesenteric arteries
Bibliographic record
Abstract
OBJECTIVE: Ovarian deficiency is known to undermine vasoprotective mechanisms and accelerate cardiovascular disease in postmenopausal women. In a rat model of menopause (aged ovariectomized [Ovx] rats), we recently revealed a vasoconstrictor pathway mediated by matrix metalloproteinases (MMPs) via cleavage of big endothelin-1 (ET-1). However, the specific impact of aging and/or Ovx on this pathway remains unknown. We hypothesized that aging exacerbates MMP-mediated vasoconstriction in an ovary-deficient state. METHODS: Young and aged female Sprague-Dawley rats, either intact or Ovx, were assessed for MMP-dependent vasoreactivity. Dose responses to big ET-1 in the absence or presence of an MMP inhibitor (GM6001) were tested on small mesenteric arteries using a pressure myograph system. MMP levels in the vascular tissue were measured by gelatin zymography. RESULTS: Both young Ovx and aged Ovx animals demonstrated a similar increase in the vasoconstriction to big ET-1 compared with the age-matched intact groups. MMP inhibition attenuated big ET-1 response in both Ovx groups and aged controls, but this effect was more pronounced in aged Ovx arteries (area under the curve reduction, 3.8 +/- 0.6 units in aged Ovx rats vs 1.5 +/- 0.5 units in young Ovx rats or 1.8 +/- 0.6 units in aged intact rats; P < 0.05). MMP-2 activity in the vascular tissue increased with age and was further augmented by Ovx. CONCLUSIONS: Regardless of age, ovarian loss increases vascular reactivity to big ET-1, which is mediated, in part, by MMP. Superimposed with advancing age, ovarian deficiency further increases the proconstrictor role of MMP, which corresponds with higher MMP-2 levels in the aging vessel wall. MMP-mediated vasoconstriction may be a mechanism contributing to vascular dysfunction in postmenopausal women.
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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 | 0.000 |
| 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 | 0.000 |
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".