期刊
JOURNAL OF CARDIAC FAILURE
卷 24, 期 4, 页码 266-275出版社
CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
DOI: 10.1016/j.cardfail.2017.12.010
关键词
LCZ696; chronic kidney disease; fibrosis; hypertrophy
资金
- Novartis [LCZ696BUSNC03T]
- Sumitomo Life Welfare and Culture Foundation
- School of Medicine Alumni, Fukuoka University
- International Postdoctoral Exchange Fellowship Program [20150050]
- Office of Research and Development of the Department of Veterans Affairs [1 IK CX 001043-01A2]
- National Institutes of Health
- Veterans Affairs Office of Research and Development
- Novartis
Background: Chronic kidney disease (CKD) is associated with cardiac hypertrophy, fibrosis, and increased risk of cardiovascular mortality. LCZ696 (sacubitril/valsartan) is a promising agent that has shown significant potential in treatment of heart failure. We hypothesized that LCZ696 is more effective than valsartan alone in the treatment of cardiovascular abnormalities associated with experimental CKD. Methods and Results: Male Sprague-Dawley rats underwent 5/6 nephrectomy and were subsequently randomized to no treatment (CKD), 30 mg/kg valsartan (VAL), or 60 mg/kg LCZ696 (LCZ). After 8 weeks, cardiovascular parameters, including markers of inflammation, oxidative stress, mitochondrial abundance/function, hypertrophy, and fibrosis, were measured. Treatment with LCZ resulted in significant improvements in the heart-body weight ratio and serum concentrations of N-terminal pro-B-type natriuretic peptide and fibroblast growth factor 23 along with improvement of kidney function. In addition, LCZ ameliorated aortic fibrosis and cardiac hypertrophy and fibrosis, reduced markers of cardiac oxidative stress and inflammation, and improved indicators of mitochondrial mass/function. Although VAL also improved some of these indices, treatment with LCZ was more effective than VAL alone. Conclusions: CKD-associated cardiovascular abnormalities, including myocardial hypertrophy, fibrosis, inflammation, oxidative stress, and mitochondrial depletion/dysfunction, were more effectively attenuated by LCZ treatment than by VAL alone.
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