Abstract 608: The Mechanisms of Preservation of Vasorelaxation Induced by Protease-Activated Receptor-2 Activation in the Aorta of Metabolic Syndrome Model Rats
Bibliographic record
Abstract
Protease-activated receptor-2 (PAR2) is activated by proteases, such as trypsin, human mast cell beta-tryptase, human kallikrein isoforms, coagulation factors VIIa and Xa, etc. PAR2 is believed to have an important role under inflammatory pathological conditions, but its role in metabolic syndrome remains uncertain. We have reported that PAR2-activating peptide, 2-furoyl-LIGRLO-amide (2fly) causes NO-mediated vasorelaxation in rat aortas similar to that observed with acetylcholine (ACh), and that 2fly-induced vasorelaxation is maintained in aortas from SHRSP.Z- Lepr fa /IzmDmcr (SHRSP.ZF) rats with metabolic syndrome, even though ACh- and sodium nitroprusside (SNP)-induced vasodilation is lower than that in control (Wistar-Kyoto rats, WKY). In this study, we assessed the mechanisms involved in the preservation of PAR2-mediated vasorelaxation in metabolic syndrome. Aortas were isolated from male WKY and SHRSP.ZF rats between 18-20 weeks of age. ACh- and 2fly-induced vasorelaxations were measured in the presence or absence of inhibitors (i.e., COX inhibitors, a TXA 2 synthase inhibitor, and a TXA 2 /PGH 2 receptor antagonist) using organ bath methods. Expression of endothelium NO synthase (eNOS) in aortas was measured by western blot analysis. Indomethacin (a non-selective COX inhibitor), SC560 (a selective COX-1 inhibitor), NS398 (a selective COX-2 inhibitor), OKY-046 (a TXA 2 synthase inhibitor), and ONO-3708 (a TXA 2 /PGH 2 receptor antagonist) did not affect both ACh- and 2fly-induced vasorelaxation in aortas of SHRSP.ZF rats as well as WKY. Expression of phosphorylated eNOS at Ser 1177 in 2fly-stimulated aortas was higher than that in ACh-stimulated ones in SHRSP.ZF rats, but there was no significant difference between these levels in WKY. Our results show that the preservation of 2fly-induced vasorelaxation observed in SHRSP.ZF rats with metabolic syndrome may be because of enhanced eNOS activation via PAR2, but not coupled to the COX pathway. Thus, preservation of PAR2-mediated vasorelaxation may be one of the key responses to maintain blood circulation under inflammatory conditions, such as metabolic syndrome.
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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 | 0.001 | 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 | 0.000 | 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".