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沙库巴曲缬沙坦对肥胖相关代谢性心脏病小鼠舒张功能的不同影响。

Differential Effects of Sacubitril/Valsartan on Diastolic Function in Mice With Obesity-Related Metabolic Heart Disease.

作者信息

Croteau Dominique, Qin Fuzhong, Chambers Jordan M, Kallick Ethan, Luptak Ivan, Panagia Marcello, Pimentel David R, Siwik Deborah A, Colucci Wilson S

机构信息

Cardiovascular Medicine Section and Myocardial Biology Unit, Boston University School of Medicine, Boston, Massachusetts.

出版信息

JACC Basic Transl Sci. 2020 Sep 9;5(9):916-927. doi: 10.1016/j.jacbts.2020.07.006. eCollection 2020 Sep.

DOI:10.1016/j.jacbts.2020.07.006
PMID:33015414
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7524781/
Abstract

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.

摘要

因高脂高糖饮食而患有肥胖症和代谢性心脏病(MHD)的小鼠,分别接受安慰剂、临床相关剂量的沙库巴曲(SAC)/缬沙坦(VAL)或等量VAL治疗4个月。SAC/VAL与VAL在以下方面存在显著差异:1)舒张功能障碍;2)间质纤维化;以及在较小程度上的3)氧化应激——所有这些方面SAC/VAL的影响更为有利。SAC/VAL和VAL同样减轻了心肌肥大并改善了心肌能量代谢。在患有肥胖相关MHD的小鼠中,抑制中性肽链内切酶对舒张功能产生有利影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/7524781/bc84a70ae015/gr7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/7524781/590946c6d52b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/7524781/3a378ac57fb0/gr4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/7524781/e7bf4a3656df/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/7524781/abe5b5c39272/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/7524781/1cd3d00d8ee9/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/7524781/590946c6d52b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/7524781/3a378ac57fb0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/7524781/9de95d1db404/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/7524781/64dd34d87b08/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/7524781/bc84a70ae015/gr7.jpg

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N Engl J Med. 2019 Oct 24;381(17):1609-1620. doi: 10.1056/NEJMoa1908655. Epub 2019 Sep 1.
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Reversal of heart failure in a chemogenetic model of persistent cardiac redox stress.持久心脏氧化还原应激的化学遗传学模型中心力衰竭的逆转。
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