Angiotensin receptor‐neprilysin inhibitor attenuates cardiac hypertrophy and improves diastolic dysfunction in a mouse model of heart failure with preserved ejection fraction
Angiotensin receptor‐neprilysin inhibitor attenuates cardiac hypertrophy and improves diastolic dysfunction in a mouse model of heart failure with preserved ejection fraction
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DOI：
10.1111/1440-1681.13672
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发表时间：
2022-05
影响因子：
2.9
通讯作者：
Yue Zhang;M. Yuan;Y. Suo;Qian Yang;Shuai Shao;Y. Li;Yuanyuan Wang;Qiankun Bao;Tong Liu
中科院分区：
文献类型：
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作者：
Yue Zhang;M. Yuan;Y. Suo;Qian Yang;Shuai Shao;Y. Li;Yuanyuan Wang;Qiankun Bao;Tong Liu
LCZ 696是一种血管紧张素受体-脑啡肽酶抑制剂，已在射血分数降低的心力衰竭（HF）患者中显示出有希望的临床疗效。然而，其对射血分数保留性心力衰竭（HFpEF）的潜在影响仍未完全了解。我们评估了LCZ 696对横向主动脉缩窄小鼠HFpEF的影响，并将其与血管紧张素受体阻断剂缬沙坦的影响进行了比较。我们发现，LCZ 696通过减少超负荷诱导的舒张功能障碍小鼠的心室肥大和纤维化来改善心脏舒张功能。此外，LCZ 696的抑制作用上级单独的缬沙坦。作为一种潜在的潜在机制，我们证明了LCZ 696是钙介导的活化T细胞核因子（NFAT）信号转导途径的有效抑制剂。因此，我们证明了LCZ 696在过载诱导的HFpEF中的保护作用，并为相关疾病提供了药物治疗策略。
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.