Smoothelin‐B: a potential target of matrix metalloproteinase (MMP)‐2 in the vasculature of endotoxemic rats
Bibliographic record
Abstract
Increased MMP-2 activity in aorta during endotoxemia caused by lipopolysaccharide (LPS) contributes to vascular hypocontractility to vasoconstrictors. Smoothelin-B, a 100 kDa filamentous protein, is an important regulator of vascular contraction. It is structurally similar to troponin T, a protein involved in cardiac myocyte contraction, which is cleaved by MMP-2. We hypothesized that smoothelin-B may be a target of MMP-2-induced vascular dysfunction in endotoxemia. Rats were treated with a non-lethal dose of LPS (4 mg/kg, i.p.) or vehicle control. Plasma nitrate + nitrite levels were 65±23 μM and 141±66 μM at 3 and 6 h following LPS, respectively, and 8.4±3.2 μM and 9.5±3.2 μM in time control rats, indicating an increase in inducible nitric oxide synthase. At both 3 and 6 h, LPS treatment activated 72 kDa MMP-2 in aorta as shown by its S-glutathiolation. At 3 h, there was a 57% decrease in smoothelin-B protein levels in LPS aorta vs. control (p<0.05). In contrast, at 6 h, smoothelin-B levels in LPS aorta were enhanced (3.4 fold vs. control, p<0.05). Immunoblot analysis for MMP-2 of anti-smoothelin-B, but not IgG1 immunoprecipitates, showed 72 kDa MMP-2 in control and especially 6 h LPS aorta extracts. Decreased smoothelin-B levels may be due to increased MMP-2 activity in aorta from 3 h LPS rats whereas a subsequent increase in 6 h LPS aortae may be a compensatory mechanism for its degradation. Grant support from CIHR.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".