Regulation of energy metabolism by combination therapy attenuates cardiac metabolic remodeling in heart failure.

Abstract:

:Cardiac metabolic remodeling is recognized as an important hallmark of heart failure (HF), while strategies that target energy metabolism have therapeutic potential in treating HF. Shen-Fu formula (S-F) is a standardized herbal preparation frequently used in clinical practice and is a promising combinatorial therapy for HF-related metabolic remodeling. Herein, we performed an untargeted multi-omics analysis using transcriptomics, proteomics, and metabolomics on HF mice induced by transverse aortic constriction (TAC). Integrated and pathway-driven analyses were used to reveal the therapeutic targets associated with S-F treatment. The cardioprotective effect and potential mechanism of S-F were verified by the results from echocardiography, hemodynamics, histopathology, and biochemical assays. As a result, S-F significantly alleviated myocardial fibrosis and hypertrophy, thus reducing the loss of heart function during adverse cardiac remodeling in TAC mice. Integrated omics analysis showed that S-F synergistically mediated the metabolic flexibility of fatty acids and glucose in cardiac energy metabolism. These effects of S-F were confirmed by the activation of AMP-activated protein kinase (AMPK) and its downstream targets in the failing heart. Collectively, our results demonstrated that S-F suppressed cardiac metabolic remodeling through activating AMPK-related pathways via energy-dependent mechanisms.

journal_name

Int J Biol Sci

authors

Huang Y,Zhang K,Jiang M,Ni J,Chen J,Li L,Deng J,Zhu Y,Mao J,Gao X,Fan G

doi

10.7150/ijbs.49520

subject

Has Abstract

pub_date

2020-10-16 00:00:00

pages

3133-3148

issue

16

issn

1449-2288

pii

ijbsv16p3133

journal_volume

16

pub_type

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