Sacubitril/Valsartan Inhibits Cardiomyocyte Hypertrophy in Angiotensin II-Induced Hypertensive Mice Independent of a Blood Pressure-Lowering Effect
Bibliographic record
Abstract
BACKGROUND: Hypertensive left ventricular hypertrophy is associated with the risk of heart failure, coronary heart disease and cerebrovascular disease. Although sacubitril/valsartan (SAC/VAL), a first-in-class angiotensin receptor neprilysin inhibitor, reduces the risks of death and hospitalization for patients with heart failure, its mechanism of action is not fully understood. We hypothesized that SAC/VAL is superior to other conventional drugs in reducing cardiac hypertrophy. METHODS: Male C57BL/6J mice were implanted with an osmotic pump containing angiotensin II (Ang II). After 7 days of Ang II infusion, mice were also treated with either SAC/VAL, valsartan, enalapril or vehicle alone each day for 2 weeks. Blood pressure measurement was done weekly, and echocardiography was performed before and 3 weeks after infusion of Ang II. Histological analyses were done using extracted heart to investigate cardiac hypertrophy and fibrosis. RESULTS: Ang II markedly elevated blood pressures in all of the treatment groups, and there were no differences in the degree of blood pressure reduction among the SAC/VAL-, valsartan- and enalapril-treated groups. Echocardiography showed that SAC/VAL significantly suppressed the increase in left ventricular (LV) wall thickness and tended to decrease LV mass. In a histological analysis, SAC/VAL inhibited Ang II-induced cardiomyocyte hypertrophy, and individual cardiomyocytes in the SAC/VAL group were smaller than those in the valsartan and enalapril groups. Although previous studies using animal models of heart failure have indicated that SAC/VAL attenuates cardiac fibrosis, we found no supporting evidence in this setting. CONCLUSIONS: SAC/VAL, valsartan and enalapril all attenuated cardiomyocyte hypertrophy in a mouse model of Ang II-induced cardiac hypertrophy. Of note, SAC/VAL most strongly suppressed hypertrophy in spite of similar blood pressure-lowering effects as valsartan and enalapril. The present study suggests that SAC/VAL may have a beneficial effect on the early stage of hypertensive heart disease.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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 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".