Journal
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
Volume 49, Issue 8, Pages 848-857Publisher
WILEY
DOI: 10.1111/1440-1681.13672
Keywords
calcium; HFpEF; hypertrophy; LCZ696; NFAT
Categories
Funding
- National Natural Science Foundation of China [81800251, 81800297, 82000272, 82170482]
- Tianjin Municipal Science and Technology Project [20JCQNJC00540, 18JCQNJC82600]
- Scientific Research Program of Tianjin Education Commission [2021KJ229]
- Tianjin Key Medical Discipline (Specialty) Construction Project
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LCZ696 improves cardiac diastolic function and reduces ventricular hypertrophy and fibrosis in mice with overload-induced HFpEF. Its inhibitory effect is superior to stand-alone valsartan. The underlying mechanism may involve the suppression of calcium-mediated NFAT signaling transduction pathways.
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.
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