Abstract
This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy.
| Original language | English |
|---|---|
| Pages (from-to) | 2645-2656 |
| Number of pages | 12 |
| Journal | Molecular and Cellular Biochemistry |
| Volume | 478 |
| Issue number | 12 |
| Early online date | 30 Mar 2023 |
| DOIs | |
| Publication status | Published - Dec 2023 |
Bibliographical note
Copyright © and Moral Rights are retained by the author(s) and/ or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This item cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder(s). The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders.This document is the author’s post-print version, incorporating any revisions agreed during the peer-review process. Some differences between the published version and this version may remain and you are advised to consult the published version if you wish to cite from it.
Funder
This work was supported by the EU Horizon 2020 research and innovation programme below grant agreement Number 777204 (SILICOFCM). This work was supported by the European Union’s Horizon 2020 research and innovation programme SGABU (Grant agreement 952603). The Commission is not responsible for any use that may be made of the information it contains.The authors appreciatively acknowledge funding from the Ministry of Education, Science and Technological Development of the Republic of Serbia (Agreement Number 451-03-68/2022-14/200378 and 451‐03‐68/2022‐14/200107). The design of the study, data collection, analyses, interpretation of data, and drafting of the manuscript do not reflect the views and opinions of the funders.Keywords
- Animal model
- Spontaneously hypertensive rats
- Neprilysin inhibition
- Entresto