Intracellular sodium elevation reprograms cardiac metabolism

被引：64

作者：

Aksentijevic, Dunja ^{[1
,6
]}

Karlstaedt, Anja ^{[2
]}

Basalay, Marina V. ^{[1
]}

O'Brien, Brett A. ^{[3
]}

Sanchez-Tatay, David ^{[1
]}

Eminaga, Seda ^{[1
]}

Thakker, Alpesh ^{[4
]}

Tennant, Daniel A. ^{[4
]}

Fuller, William ^{[5
]}

Eykyn, Thomas R. ^{[3
]}

Taegtmeyer, Heinrich ^{[2
]}

Shattock, Michael J. ^{[1
]}

机构：

[1] Kings Coll London, Sch Cardiovasc & Med Sci, British Heart Fdn Ctr Res Excellence, Rayne Inst,St Thomas Hosp, London, England

[2] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Div Cardiol, Dept Internal Med, Houston, TX 77030 USA

[3] Kings Coll London, Sch Biomed Engn & Imaging Sci, St Thomas Hosp, London SE1 7EH, England

[4] Univ Birmingham, Coll Med & Dent Sci, Inst Metab & Syst Res, Birmingham B15 2TT, W Midlands, England

[5] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland

[6] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Charterhouse Sq, London EC1M 6BQ, England

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

英国惠康基金; 英国工程与自然科学研究理事会; 英国医学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

MITOCHONDRIAL CA2+ UPTAKE; OXIDATIVE-PHOSPHORYLATION; CONTRACTILE FUNCTION; HEART-FAILURE; ATPASE; DEHYDROGENASE; HOMEOSTASIS; GLYCOLYSIS; EXPRESSION; EXCHANGER;

D O I：

10.1038/s41467-020-18160-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Intracellular Na elevation in the heart is a hallmark of pathologies where both acute and chronic metabolic remodelling occurs. Here, we assess whether acute (75 mu M ouabain 100 nM blebbistatin) or chronic myocardial Na, load (PLM 3 sA mouse) are causally linked to metabolic remodelling and whether the failing heart shares a common Na-mediated metabolic 'fingerprint'. Control (PLMWT), transgenic (PLM3SA), ouabain-treated and hypertrophied Langendorff-perfused mouse hearts are studied by Na-23, P-31, C-13 NMR followed by H-1-NMR metabolomic profiling. Elevated Na, leads to common adaptive metabolic alterations preceding energetic impairment: a switch from fatty acid to carbohydrate metabolism and changes in steady-state metabolite concentrations (glycolytic, anaplerotic, Krebs cycle intermediates). Inhibition of mitochondrial Na/Ca exchanger by CGP37157 ameliorates the metabolic changes. In silico modelling indicates altered metabolic fluxes (Krebs cycle, fatty acid, carbohydrate, amino acid metabolism). Prevention of Na, overload or inhibition of Na/Ca-mito may be a new approach to ameliorate metabolic dysregulation in heart failure.

引用

页数：14

共 51 条

[1]

Is there a causal link between intracellular Na elevation and metabolic remodelling in cardiac hypertrophy? [J].