Cardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts

Abstract Left ventricular remodeling due to pressure overload is associated with poor prognosis. Sacubitril/valsartan is the first-in-class Angiotensin Receptor Neprilysin Inhibitor and has been demonstrated to have superior beneficial effects in the settings of heart failure. The aim of this study...

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Autores principales:	Xiaofei Li, Julie Braza, Ulrike Mende, Gaurav Choudhary, Peng Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/07e6e0112c174e9b92b92f4ed2307745
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spelling	oai:doaj.org-article:07e6e0112c174e9b92b92f4ed23077452021-12-02T15:10:46ZCardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts10.1038/s41598-021-95988-32045-2322https://doaj.org/article/07e6e0112c174e9b92b92f4ed23077452021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95988-3https://doaj.org/toc/2045-2322Abstract Left ventricular remodeling due to pressure overload is associated with poor prognosis. Sacubitril/valsartan is the first-in-class Angiotensin Receptor Neprilysin Inhibitor and has been demonstrated to have superior beneficial effects in the settings of heart failure. The aim of this study was to determine whether sacubitril/valsartan has cardioprotective effect in the early intervention of pressure overloaded hearts and whether it is superior to valsartan alone. We induced persistent left ventricular pressure overload in rats by ascending aortic constriction surgery and orally administrated sacubitril/valsartan, valsartan, or vehicle one week post operation for 10 weeks. We also determined the effects of sacubitril/valsartan over valsartan on adult ventricular myocytes and fibroblasts that were isolated from healthy rats and treated in culture. We found that early intervention with sacubitril/valsartan is superior to valsartan in reducing pressure overload-induced ventricular fibrosis and in reducing angiotensin II-induced adult ventricular fibroblast activation. While neither sacubitril/valsartan nor valsartan changes cardiac hypertrophy development, early intervention with sacubitril/valsartan protects ventricular myocytes from mitochondrial dysfunction and is superior to valsartan in reducing mitochondrial oxidative stress in response to persistent left ventricular pressure overload. In conclusion, our findings demonstrate that sacubitril/valsartan has a superior cardioprotective effect over valsartan in the early intervention of pressure overloaded hearts, which is independent of the reduction of left ventricular afterload. Our study provides evidence in support of potential benefits of the use of sacubitril/valsartan in patients with resistant hypertension or in patients with severe aortic stenosis.Xiaofei LiJulie BrazaUlrike MendeGaurav ChoudharyPeng ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaofei Li Julie Braza Ulrike Mende Gaurav Choudhary Peng Zhang Cardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts
description	Abstract Left ventricular remodeling due to pressure overload is associated with poor prognosis. Sacubitril/valsartan is the first-in-class Angiotensin Receptor Neprilysin Inhibitor and has been demonstrated to have superior beneficial effects in the settings of heart failure. The aim of this study was to determine whether sacubitril/valsartan has cardioprotective effect in the early intervention of pressure overloaded hearts and whether it is superior to valsartan alone. We induced persistent left ventricular pressure overload in rats by ascending aortic constriction surgery and orally administrated sacubitril/valsartan, valsartan, or vehicle one week post operation for 10 weeks. We also determined the effects of sacubitril/valsartan over valsartan on adult ventricular myocytes and fibroblasts that were isolated from healthy rats and treated in culture. We found that early intervention with sacubitril/valsartan is superior to valsartan in reducing pressure overload-induced ventricular fibrosis and in reducing angiotensin II-induced adult ventricular fibroblast activation. While neither sacubitril/valsartan nor valsartan changes cardiac hypertrophy development, early intervention with sacubitril/valsartan protects ventricular myocytes from mitochondrial dysfunction and is superior to valsartan in reducing mitochondrial oxidative stress in response to persistent left ventricular pressure overload. In conclusion, our findings demonstrate that sacubitril/valsartan has a superior cardioprotective effect over valsartan in the early intervention of pressure overloaded hearts, which is independent of the reduction of left ventricular afterload. Our study provides evidence in support of potential benefits of the use of sacubitril/valsartan in patients with resistant hypertension or in patients with severe aortic stenosis.
format	article
author	Xiaofei Li Julie Braza Ulrike Mende Gaurav Choudhary Peng Zhang
author_facet	Xiaofei Li Julie Braza Ulrike Mende Gaurav Choudhary Peng Zhang
author_sort	Xiaofei Li
title	Cardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts
title_short	Cardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts
title_full	Cardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts
title_fullStr	Cardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts
title_full_unstemmed	Cardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts
title_sort	cardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/07e6e0112c174e9b92b92f4ed2307745
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Cardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts

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