Angiotensin receptor-neprilysin inhibitor attenuates cardiac hypertrophy and improves diastolic dysfunction in a mouse model of heart failure with preserved ejection fraction

被引：4

作者：

Zhang, Yue ^{[1
]}

Yuan, Meng ^{[1
]}

Suo, Ya ^{[1
]}

Yang, Qian ^{[1
]}

Shao, Shuai ^{[1
]}

Li, Ying ^{[1
]}

Wang, Yuanyuan ^{[1
]}

Bao, Qiankun ^{[1
]}

Liu, Tong ^{[1
]}

Li, Guangping ^{[1
]}

机构：

[1] Tianjin Med Univ, Tianjin Inst Cardiol, Tianjin Key Lab Ion Mol Funct Cardiovasc Dis, Dept Cardiol,Hosp 2, Tianjin 300211, Peoples R China

来源：

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY | 2022年 / 49卷 / 08期

基金：

中国国家自然科学基金;

关键词：

calcium; HFpEF; hypertrophy; LCZ696; NFAT; STROMAL INTERACTION MOLECULE-1; NATRIURETIC PEPTIDE SYSTEM; MYOCARDIAL-INFARCTION; DOUBLE-BLIND; LCZ696; DISEASE; FIBROSIS; BIOLOGY;

D O I：

10.1111/1440-1681.13672

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

LCZ696, an angiotensin receptor-neprilysin inhibitor, has shown promising clinical efficacy in patients with heart failure (HF) with reduced ejection fraction. However, its potential effects on heart failure with preserved ejection fraction (HFpEF) are still not fully understood. We evaluated the effect of LCZ696 on HFpEF in transverse aortic constriction mice and compared it with the effect of the angiotensin receptor blocker, valsartan. We found that LCZ696 improved cardiac diastolic function by reducing ventricular hypertrophy and fibrosis in mice with overload-induced diastolic dysfunction. In addition, there was superior inhibition of LCZ696 than stand-alone valsartan. As a potential underlying mechanism, we demonstrated that LCZ696 behaves as a potent suppressor of calcium-mediated calcineurin-nuclear factor of activated T cells (NFAT) signalling transduction pathways. Hence, we demonstrated the protective effects of LCZ696 in overload-induced HFpEF and provided a pharmaceutical therapeutic strategy for related diseases.

引用

页码：848 / 857

页数：10

共 55 条

[21] HYDROLYSIS OF HUMAN AND PIG BRAIN NATRIURETIC PEPTIDES, URODILATION, C-TYPE NATRIURETIC PEPTIDE AND SOME C-RECEPTOR LIGANDS BY ENDOPEPTIDASE-24.11 [J].