Metabolomic analysis of serum and myocardium in compensated heart failure after myocardial infarction

LIFE SCIENCES

卷:221

Article

McKirnan, M. Dan^1,2  Ichikawa, Yasuhiro¹  Zhang, Zheng¹  Zemljic-Harpf, Alice E.¹  Fan, Sili³  Barupal, Dinesh Kumar³  Patel, Hemal H.¹  Hammond, H. Kirk²  Roth, David M.¹ 

[1] Univ Calif San Diego, Dept Anesthesiol, Vet Affairs San Diego Healthcare Syst, San Diego, CA 92103 USA

[2] Univ Calif San Diego, Dept Med, Vet Affairs San Diego Healthcare Syst, San Diego, CA 92103 USA

[3] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA

关键词: Metabolomics;    Myocardial infarction;    Heart failure;    Taurine;    Inosine;    Myo-inositol;    BCAA;   

DOI  :  10.1016/j.lfs.2019.01.040

来源: Elsevier

【 摘 要 】

Aims: To determine the metabolic adaptations to compensated heart failure using a reproducible model of myocardial infarction and an unbiased metabolic screen. To address the limitations in sample availability and model variability observed in preclinical and clinical metabolic investigations of heart failure. Main methods: Metabolomic analysis was performed on serum and myocardial tissue from rabbits after myocardial infarction (MI) was induced by cryo-injury of the left ventricular free wall. Rabbits followed for 12 weeks after MI exhibited left ventricular dilation and depressed systolic function as determined by echocardiography. Serum and tissue from the viable left ventricular free wall, interventricular septum and right ventricle were analyzed using a gas chromatography time of flight mass spectrometry-based untargeted metabolomics assay for primary metabolites. Key findings: Unique results included: a two-three-fold increase in taurine levels in all three ventricular regions of MI rabbits and similarly, the three regions had increased inosine levels compared to sham controls. Reduced myocardial levels of myo-inositol in the myocardium of MI animals point to altered phospholipid metabolism and membrane receptor function in heart failure. Metabolite profiles also provide evidence for responses to oxidative stress and an impairment in TCA cycle energy production in the failing heart. Significance: Our results revealed metabolic changes during compensated cardiac dysfunction and suggest potential targets for altering the progression of heart failure.

【 授权许可】

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