Regulation of energy metabolism by combination therapy attenuates cardiac metabolic remodeling in heart failure.
Regulation of energy metabolism by combination therapy attenuates cardiac metabolic remodeling in heart failure.
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通过联合治疗调节能量代谢可减弱心力衰竭中的心脏代谢重塑
DOI：
10.7150/ijbs.49520
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发表时间：
2020
影响因子：
9.2
通讯作者：
Fan G
中科院分区：
文献类型：
--
作者：
Huang Y;Zhang K;Jiang M;Ni J;Chen J;Li L;Deng J;Zhu Y;Mao J;Gao X;Fan G
心脏代谢重塑被认为是心力衰竭 (HF) 的重要标志，而针对能量代谢的策略在治疗 HF 方面具有治疗潜力。参附方（S-F）是临床实践中常用的标准化草药制剂，是治疗心力衰竭相关代谢重塑的一种有前途的组合疗法。在此，我们利用转录组学、蛋白质组学和代谢组学对横向主动脉缩窄（TAC）诱导的心力衰竭小鼠进行了非靶向多组学分析。综合和路径驱动分析用于揭示与 S-F 治疗相关的治疗靶点。 S-F的心脏保护作用和潜在机制通过超声心动图、血流动力学、组织病理学和生化检测的结果得到验证。结果，S-F显着减轻了心肌纤维化和肥大，从而减少了TAC小鼠不良心脏重塑过程中心脏功能的丧失。综合组学分析表明，S-F 协同介导脂肪酸和葡萄糖在心脏能量代谢中的代谢灵活性。 S-F 的这些作用通过 AMP 激活蛋白激酶 (AMPK) 及其下游靶标在衰竭心脏中的激活得到证实。总的来说，我们的结果表明，S-F 通过能量依赖机制激活 AMPK 相关途径，从而抑制心脏代谢重塑。
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.
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影响因子：
20.1
作者：
Doenst T;Nguyen TD;Abel ED
通讯作者：
Abel ED
影响因子：
20.1
作者：
Rowe GC;Jiang A;Arany Z
通讯作者：
Arany Z
影响因子：
4
作者：
Li L;Pan CS;Yan L;Cui YC;Liu YY;Mu HN;He K;Hu BH;Chang X;Sun K;Fan JY;Huang L;Han JY
通讯作者：
Han JY
影响因子：
16.6
作者：
Lau E;Cao Q;Lam MPY;Wang J;Ng DCM;Bleakley BJ;Lee JM;Liem DA;Wang D;Hermjakob H;Ping P
通讯作者：
Ping P
影响因子：
20.1
作者：
Kolwicz SC Jr;Olson DP;Marney LC;Garcia-Menendez L;Synovec RE;Tian R
通讯作者：
Tian R