Dataset Information

Cardioprotective Effects of LCZ696 (Sacubitril/Valsartan) After Experimental Acute Myocardial Infarction.

ABSTRACT: LCZ696 (sacubitril/valsartan) can lower the risk of cardiovascular events in chronic heart failure. However, it is unclear whether LCZ696 can improve prognosis in patients with acute myocardial infarction (MI). The present study shows that LCZ696 can prevent cardiac rupture after MI, probably due to the suppression of pro-inflammatory cytokines, matrix metalloproteinase-9 activity and aldosterone production, and enhancement of natriuretic peptides in mice. These findings suggest the mechanistic insight of cardioprotective effects of LCZ696 against acute MI, resulting in the belief that LCZ696 might be useful clinically to improve survival after acute MI.

SUBMITTER: Ishii M

PROVIDER: S-EPMC6059351 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Cardioprotective Effects of LCZ696 (Sacubitril/Valsartan) After Experimental Acute Myocardial Infarction.

Ishii Masanobu M Kaikita Koichi K Sato Koji K Sueta Daisuke D Fujisue Koichiro K Arima Yuichiro Y Oimatsu Yu Y Mitsuse Tatsuro T Onoue Yoshiro Y Araki Satoshi S Yamamuro Megumi M Nakamura Taishi T Izumiya Yasuhiro Y Yamamoto Eiichiro E Kojima Sunao S Kim-Mitsuyama Shokei S Ogawa Hisao H Tsujita Kenichi K

JACC. Basic to translational science 20171225 6

LCZ696 (sacubitril/valsartan) can lower the risk of cardiovascular events in chronic heart failure. However, it is unclear whether LCZ696 can improve prognosis in patients with acute myocardial infarction (MI). The present study shows that LCZ696 can prevent cardiac rupture after MI, probably due to the suppression of pro-inflammatory cytokines, matrix metalloproteinase-9 activity and aldosterone production, and enhancement of natriuretic peptides in mice. These findings suggest the mechanistic ...[more]

PMID: 30062181

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Project description:Objectives: To investigate the effect and mechanism of sacubitril/valsartan on myocardial fibrosis in rats following experimental myocardial infarction and in TGF-β1-treated myocardial fibroblasts. Methods: Male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to establish myocardial infarction and intragastrically fed vehicle, valsartan (Val, 32 mg/kg, once-daily) or sacubitril/valsartan (Sac/Val, 68 mg/kg, once-daily) for 4 weeks. In parallel, myocardial fibroblasts (MFs) isolated from neonatal SD rats were exposed to hypoxia and treated with TGF-β1 (5 ng/ml) plus vehicle, Val (107-10-5 M) or Sac/Val (107-105 M). Rat cardiac function and fibrosis were measured by echocardiography and histological method, respectively. MFs viability and collagen synthesis were determined by cell counting kit-8 and enzyme-linked immunosorbent assay, respectively. Protein expressions of TGF-β1, Smad3, phosphorylated Smad3 (p-Smad3), and p-Smad3 subcellular localization were detected by immunoblotting and immunocytochemistry. Results: Sac/Val significantly improved cardiac structure and function in rats after myocardial infarction, including decreased left ventricular end-diastolic diameter and interventricular septal thickness, increased ejection fraction, and reduced myocardial collagen volume fraction and type Ⅰ and type Ⅲ collagen levels, and this effect was superior to that of Val. Besides, Sac/Val inhibited myocardial TGF-β1 and p-Smad3 protein expression better than Val. Mechanically, Sac/Val significantly attenuated TGF-β1-induced proliferation and collagen synthesis of MFs, and inhibit Smad3 phosphorylation and nucleus translocation, and this effect outperformed Val. Overexpression and silencing of Smad3 enhanced and reversed the inhibitory effects of Sac/Val on TGF-β1-induced collagen synthesis by MFs, respectively. Conclusions: Sacubitril/valsartan improves cardiac function and fibrosis in rats after experimental myocardial infarction, and this effect is related to the inhibition of collagen synthesis in myocardial fibroblasts by inhibiting the TGF/Smads signaling pathway.

Dataset Information

Cardioprotective Effects of LCZ696 (Sacubitril/Valsartan) After Experimental Acute Myocardial Infarction.

Publications

Cardioprotective Effects of LCZ696 (Sacubitril/Valsartan) After Experimental Acute Myocardial Infarction.

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