Journal
JACC-BASIC TO TRANSLATIONAL SCIENCE
Volume 5, Issue 9, Pages 916-927Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2020.07.006
Keywords
diastolic; neprilysin; obesity
Categories
Funding
- Novartis [SAC/VAL696BUSNC22T]
- American Heart Association Fellow-to-Faculty Award [15FTF25890062]
- National Institutes of Health [HL-064750, K08 HL123744]
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Mice with obesity and metabolic heart disease (MHD) due to a high-fat, high-sucrose diet were treated with placebo, a clinically relevant dose of sacubitril (SAC)/valsartan (VAL), or an equivalent dose of VAL for 4 months. There were striking differences between SAC/VAL and VAL with regard to: 1) diastolic dysfunction; 2) interstitial fibrosis; and to a lesser degree; 3) oxidative stress-all of which were more favorably affected by SAC/VAL. SAC/VAL and VAL similarly attenuated myocardial hypertrophy and improved myocardial energetics. In mice with obesity-related MHD, neprilysin inhibition exerts favorable effects on diastolic function. (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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