1H-NMR-based metabolic analysis of human serum reveals novel markers of myocardial energy expenditure in heart failure patients

• Published in: PloS one Vol. 9; no. 2; p. e88102
• Main Authors: Du, Zhiyong, Shen, Anna, Huang, Yuli, Su, Liang, Lai, Wenyan, Wang, Peng, Xie, Zhibing, Xie, Zhiquan, Zeng, Qingchun, Ren, Hao, Xu, Dingli
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.02.2014; Public Library of Science (PLoS)
• Subjects: 3-Hydroxybutyric Acid - blood; 3-Hydroxybutyric Acid - metabolism; Acetone; Acetone - blood; Acetone - metabolism; Adult; Aged; Aged, 80 and over; Angiotensin; Angiotensin converting enzyme; Angiotensin-converting enzyme inhibitors; Bioindicators; Biology; Biomarkers; Cardiology; Cardiovascular disease; Cardiovascular diseases; Chemistry; Coronary vessels; Dehydrogenases; Diabetes; Diuretics; Doppler effect; Echocardiography; Education; Energy expenditure; Energy Metabolism; Enzyme inhibitors; Failure analysis; Fatty acids; Female; Health aspects; Heart; Heart diseases; Heart failure; Heart Failure - blood; Heart Failure - metabolism; Heart Failure - pathology; Hospitals; Humans; Laboratories; Least squares method; Magnetic resonance; Male; Medicine; Metabolism; Metabolites; Metabolomics; Metabolomics - methods; Middle Aged; Mortality; Myocardium - metabolism; Myocardium - pathology; NMR; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular - methods; Oxidation; Patients; Peptidyl-dipeptidase A; Regression analysis; Serum - metabolism; Signal processing; Spectrum analysis; Statins; Succinic Acid - blood; Succinic Acid - metabolism; Tomography; Type 2 diabetes; Urine; Ventricle
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088102

Elevated myocardial energy expenditure (MEE) is related with reduced left ventricular ejection fraction, and has also been documented as an independent predictor of cardiovascular mortality. However, the serum small-molecule metabolite profiles and pathophysiological mechanisms of elevated MEE in heart failure (HF) are still lacking. Herein, we used 1H-NMR-based metabolomics analysis to screen for potential biomarkers of MEE in HF. A total of 61 subjects were enrolled, including 46 patients with heart failure and 15 age-matched controls. Venous serum samples were collected from subjects after an 8-hour fast. An INOVA 600 MHz nuclear magnetic resonance spectrometer with Carr-Purcell-Melboom-Gill (CPMG) pulse sequence was employed for the metabolomics analysis and MEE was calculated using colored Doppler echocardiography. Metabolomics data were processed using orthogonal signal correction and regression analysis was performed using the partial least squares method. The mean MEE levels of HF patients and controls were 139.61±58.18 cal/min and 61.09±23.54 cal/min, respectively. Serum metabolomics varied with MEE changed, and 3-hydroxybutyrate, acetone and succinate were significantly elevated with the increasing MEE. Importantly, these three metabolites were independent of administration of angiotensin converting enzyme inhibitor, β-receptor blockers, diuretics and statins (P>0.05). These results suggested that in patients with heart failure, MEE elevation was associated with significant changes in serum metabolomics profiles, especially the concentration of 3-hydroxybutyrate, acetone and succinate. These compounds could be used as potential serum biomarkers to study myocardial energy mechanism in HF patients.