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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\u2010induced diastolic dysfunction. In addition, there was superior inhibition of LCZ696 than stand\u2010alone valsartan. As a potential underlying mechanism, we demonstrated that LCZ696 behaves as a potent suppressor of calcium\u2010mediated calcineurin\u2010nuclear factor of activated T cells (NFAT) signalling transduction pathways. Hence, we demonstrated the protective effects of LCZ696 in overload\u2010induced HFpEF and provided a pharmaceutical therapeutic strategy for related diseases.<\/jats:p>","DOI":"10.1111\/1440-1681.13672","type":"journal-article","created":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T05:09:30Z","timestamp":1653109770000},"page":"848-857","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Angiotensin receptor\u2010neprilysin inhibitor attenuates cardiac hypertrophy and improves diastolic dysfunction in a mouse model of heart failure with preserved ejection fraction"],"prefix":"10.1111","volume":"49","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular disease, Department of Cardiology Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University  Tianjin 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