Multi-Omics Approach Profiling Metabolic Remodeling in Early Systolic Dysfunction and in Overt Systolic Heart Failure.
Multi-Omics Approach Profiling Metabolic Remodeling in Early Systolic Dysfunction and in Overt Systolic Heart Failure.
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DOI：
10.3390/ijms23010235
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发表时间：
2021-12-26
影响因子：
5.6
通讯作者：
Delafontaine P
中科院分区：
文献类型：
--
作者：
Chaanine AH;Higgins L;Markowski T;Harman J;Kachman M;Burant C;Navar LG;Busija D;Delafontaine P
代谢重构在心力衰竭（HF）的病理生理过程中起着重要作用。我们试图在早期收缩功能障碍（MOD）和明显收缩性HF（SHF）的两种大鼠模型中表征代谢重塑和相关信号通路。使用液相色谱-质谱法对来自Sham、MOD和SHF的左心室心肌组织进行串联质量标签标记的鸟枪蛋白质组学、磷酸化-（p）-蛋白质组学和非靶向代谢组学分析，每组n = 3个生物样品。与假手术相比，MOD（125）和SHF（328）中线粒体蛋白主要下调。其中82%（103/125）和66%（218/328）参与代谢和呼吸。氧化磷酸化、线粒体脂肪酸β-氧化、Krebs循环、支链氨基酸和氨基酸（谷氨酰胺和色氨酸）降解是高度富集的代谢途径，在SHF > MOD中减少。糖原和葡萄糖降解在MOD中主要增加，而糖酵解和丙酮酸代谢在SHF中主要减少。在MOD中内质网-mt界面处的PKA信号传导减弱，而在SHF与Sham中总体PKA和AMPK细胞信号传导减弱。总之，代谢重构在心肌重构中起重要作用。PKA和AMPK信号转导交叉调控向SHF进展中的代谢重构。
Metabolic remodeling plays an important role in the pathophysiology of heart failure (HF). We sought to characterize metabolic remodeling and implicated signaling pathways in two rat models of early systolic dysfunction (MOD), and overt systolic HF (SHF). Tandem mass tag-labeled shotgun proteomics, phospho-(p)-proteomics, and non-targeted metabolomics analyses were performed in left ventricular myocardium tissue from Sham, MOD, and SHF using liquid chromatography–mass spectrometry, n = 3 biological samples per group. Mitochondrial proteins were predominantly down-regulated in MOD (125) and SHF (328) vs. Sham. Of these, 82% (103/125) and 66% (218/328) were involved in metabolism and respiration. Oxidative phosphorylation, mitochondrial fatty acid β-oxidation, Krebs cycle, branched-chain amino acids, and amino acid (glutamine and tryptophan) degradation were highly enriched metabolic pathways that decreased in SHF > MOD. Glycogen and glucose degradation increased predominantly in MOD, whereas glycolysis and pyruvate metabolism decreased predominantly in SHF. PKA signaling at the endoplasmic reticulum–mt interface was attenuated in MOD, whereas overall PKA and AMPK cellular signaling were attenuated in SHF vs. Sham. In conclusion, metabolic remodeling plays an important role in myocardial remodeling. PKA and AMPK signaling crosstalk governs metabolic remodeling in progression to SHF.
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影响因子：
20.1
作者：
Doenst T;Nguyen TD;Abel ED
通讯作者：
Abel ED
DOI：
10.1073/pnas.1806318115
发表时间：
2018-07-10
影响因子：
11.1
作者：
Burdyga A;Surdo NC;Monterisi S;Di Benedetto G;Grisan F;Penna E;Pellegrini L;Zaccolo M;Bortolozzi M;Swietach P;Pozzan T;Lefkimmiatis K
通讯作者：
Lefkimmiatis K
DOI：
10.33594/000000151
发表时间：
2019-01-01
期刊：
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子：
--
作者：
Castillo, Elena C;Morales, Jose A;Garcia-Rivas, Gerardo
通讯作者：
Garcia-Rivas, Gerardo
影响因子：
10.8
作者：
Doenst, Torsten;Pytel, Gracjan;Schwarzer, Michael
通讯作者：
Schwarzer, Michael
影响因子：
7.1
作者：
Fernandez-Marcos, Pablo J.;Auwerx, Johan
通讯作者：
Auwerx, Johan