Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited. Metabolomics: a new era in cardiology? Giuseppe Mercuro a , Pier P. Bassareo a , Martino Deidda a , Christian Cadeddu a , Luigi Barberini a and Luigi Atzori b The metabolome represents the collection of all metabolites in a biological cell, tissue, organ or organism, which are the end-products of cellular processes. Metabolomics is the systematic study of small-molecule metabolite profiles that specific cellular processes leave behind. RNA messenger gene expression data and proteomic analyses do not tell the whole story of what might be happening in a cell. Metabolic profiling, in turn, amplifies changes both in the proteome and the genome, and represents a more accurate approximation to the phenotype of an organism in health and disease. In this article, we have provided a description of metabolomics, in the presence of other, more familiar ‘omics’ disciplines, such as genomics and proteomics. In addition, we have reviewed the current rationale for metabolomics in cardiology, its basic methodology and the data actually available in human studies in this discipline. The discussed topics highlight the importance of being able to use the metabolomics information in order to understand disease mechanisms from a systems biology perspective as a noninvasive approach to diagnose, grade and treat cardiovascular diseases. J Cardiovasc Med 2011, 12:800–805 Keywords: cardiology, diagnostics, metabolomics, therapeutics a Department of Cardiovascular and Neurological Sciences and b Department of Toxicology, University of Cagliari, Monserrato, Italy Correspondence to Giuseppe Mercuro, MD, Department of Cardiovascular and Neurological Sciences, University of Cagliari, Asse didattico Medicina – SS Sestu KM 0.700, 09042 Monserrato, Italy Tel: +39 070 675 4955; e-mail: mercuro@medicina.unica.it Received 22 September 2010 Revised 22 June 2011 Accepted 29 June 2011 Introduction The ‘omics’ technologies are a group of analytical meth- odologies applied in the study of molecules such as genes, transcripts, proteins and metabolites constituting a cell, tissue or organism. Genomics may be described as the comprehensive analysis of DNA structure and function. Understanding biological diversity at the whole-genome level will yield insight into the origins of individual traits and disease susceptibility. Proteomics involves the sys- tematic study of proteins in order to provide a compre- hensive view of the structure, function and regulation of biological systems. Genomics not only involves the study of small nuclear proteins and mutations in DNA, but also includes, through the subdiscipline of transcriptomics, the comprehensive analysis of gene expression in a cell. Genes alone do not predict phenotypes, which are the results of the genes but also of physiopathological con- ditions and environmental influences. As a result, geno- mics, transcriptomics and proteomics merely indicate the potential causes for a phenotypic response, but they cannot predict what will happen at the next level. For these reasons, we must consider the metabolomics (or metabonomics), the youngest but also the most promising of the ‘omics’ disciplines. Metabolomics is the study of the small-molecule metabolite profile of a biological organism, with the metabolome representing the collec- tion of all metabolites. Metabolomics provides a func- tional view of an organism as determined by the sum of its genes, RNA, proteins and environmental factors includ- ing, for example, nutrition, drugs and treatments. So, we can consider metabolomics as a functional genomics and metabolites the stones on which are built up the cellular processes (Fig. 1). It reflects the true functional endpoints of biological events. Also, whereas the human organism consists of some 30 000 genes, 150 000 transcripts and one million proteins, the metabolome consists of some 6500 molecules only and is easier to interpret. Metabolomics is not confined to pathological conditions involving meta- bolic disorders. A search in MEDLINE indicates the exponential growth of this discipline (Fig. 2). Still, a search including also the term Cardiovasc generated fewer than 100 publications. This new approach in describing the phenotype of a cell, tissue or organism through the full set of their metabolites has been referred to as metabonomics or metabolomics. Specifically, meta- bonomics has been defined as the ‘quantitative measure- ment of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification’, whereas metabolomics is the study of ‘the complete set of metabolites/low-molecular-weight inter- mediates, which are context dependent, varying accord- ing to the physiology, developmental or pathological state of the cell, tissue, organ or organism’. 1–4 These two terms are currently used interchangeably and becoming synon- ymous. A full review has been recently written by Dunn et al. 5 In this article, we prefer to use the term metabo- lomics in order to identify all the approaches, whereby a global analytical tool is used in conjunction with pattern Clinical review 1558-2027 ß 2011 Italian Federation of Cardiology DOI:10.2459/JCM.0b013e32834a658f