Metabolomic distinction and insights into the pathogenesis of human primary dilated cardiomyopathy
Article first published online: 14 DEC 2010
© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 41, Issue 5, pages 527–538, May 2011
How to Cite
Alexander, D., Lombardi, R., Rodriguez, G., Mitchell, M. M. and Marian, A. J. (2011), Metabolomic distinction and insights into the pathogenesis of human primary dilated cardiomyopathy. European Journal of Clinical Investigation, 41: 527–538. doi: 10.1111/j.1365-2362.2010.02441.x
- Issue published online: 6 APR 2011
- Article first published online: 14 DEC 2010
- Received 12 August 2010; accepted 2 November 2010
- heart failure;
Eur J Clin Invest 2011; 41 (5): 527–538
Background Metabolomics, the comprehensive profile of small-molecule metabolites found in biological specimens, has the potential to provide insights into the pathogenesis of disease states and lead to the identification of new biomarkers.
Methods and Results We analysed 451 plasma metabolites by liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy in 39 patients with primary dilated cardiomyopathy (DCM) and 31 age-, sex- and body mass index-matched controls. Sixty-one metabolites were significantly different between primary DCM and control individuals [false discovery rate (FDR) < 0·05]. Plasma levels of steroid metabolites, glutamine, threonine and histidine were reduced while levels of citric acid cycle intermediates and lipid β-oxidation products were increased in patients with primary DCM when compared to controls. Medications, particularly furosemide and angiotensin-1 converting enzyme-1 inhibitors, had significant effects on the plasma metabolites. Reduced levels of glutamine in conjunction with increased 3-methyhistidine and prolylhydroxyproline levels suggested enhanced myofibrillar and collagen degradation in DCM patients. Likewise, increased stachydrine and reduced indole-3-propionate implicated a role for intestinal-derived antioxidant molecules. Changes in steroid metabolites were notable for the loss of metabolic distinction between men and women in patients with primary DCM. Cortisol and cortisone levels were increased while androgen metabolites were decreased significantly, implying metabolic ‘feminization’ of men with primary DCM.
Conclusions Metabolomic profiling identifies biologically active metabolites that could serve as markers of primary DCM and impart protective or harmful effects on cardiac structure and function.