Acute inhibition of Rho-kinase improves cardiac contractile function in streptozotocin-diabetic rats
Why this work is in the frame
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Bibliographic record
Abstract
OBJECTIVE: The purpose of the present study was to determine whether increased activation of the RhoA/Rho-kinase (ROCK) pathway occurs in diabetic cardiomyopathy and whether acute inhibition of this pathway improves contractile function of the diabetic heart. METHODS: Male Wistar rats were made diabetic with streptozotocin. Twelve to fourteen weeks later, the effects of acute administration of the ROCK inhibitors Y-27632 and H-1152 on cardiac contractile function were measured both in vitro, in isolated working hearts, and in vivo, using echocardiography. Changes in the expression and activity of RhoA, and the effect of ROCK inhibition on changes in the phosphorylation of the downstream target of ROCK, LIM kinase 2, and on actin polymerization in diabetic hearts were also determined. RESULTS: Perfusion of isolated working hearts from diabetic rats with Y-27632 or H-1152 acutely improved left ventricle developed pressure and the rates of contraction and relaxation. Acute administration of H-1152 also significantly improved the percent fraction shortening, an index of left ventricle contractility, in vivo in diabetic rats. The expression and activity of RhoA in cardiomyocytes from diabetic rats were significantly increased, as was the phosphorylation of LIM kinase 2. This was associated with an increase in actin polymerization (the F-actin to G-actin ratio). Both the increase in LIM kinase 2 phosphorylation and actin polymerization were attenuated by ROCK inhibition. CONCLUSIONS: These data suggest that activation of the RhoA/ROCK signaling pathway plays a critical role in the development of diabetic cardiomyopathy, and that ROCK is an excellent therapeutic target in the treatment of this condition.
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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 | 0.008 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| 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) | 0.000 | 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 it