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  • Review Article
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Metabolomics as a tool for cardiac research

Abstract

Metabolomics represents a paradigm shift in metabolic research, away from approaches that focus on a limited number of enzymatic reactions or single pathways, to approaches that attempt to capture the complexity of metabolic networks. Additionally, the high-throughput nature of metabolomics makes it ideal to perform biomarker screens for diseases or follow drug efficacy. In this Review, we explore the role of metabolomics in gaining mechanistic insight into cardiac disease processes, and in the search for novel biomarkers. High-resolution NMR spectroscopy and mass spectrometry are both highly discriminatory for a range of pathological processes affecting the heart, including cardiac ischemia, myocardial infarction, and heart failure. We also discuss the position of metabolomics in the range of functional-genomic approaches, being complementary to proteomic and transcriptomic studies, and having subdivisions such as lipidomics (the study of intact lipid species). In addition to techniques that monitor changes in the total sizes of pools of metabolites in the heart and biofluids, the role of stable-isotope methods for monitoring fluxes through pathways is examined. The use of these novel functional-genomic tools to study metabolism provides a unique insight into cardiac disease progression.

Key Points

  • Metabolomics (also called metabonomics) is the general measurement of the metabolites found within a cell, tissue, biofluid, or organism

  • Although no single analytical tool can measure all the metabolites within an organism, NMR spectroscopy and mass spectrometry can profile wide ranges of metabolites

  • Metabolomics is hypothesis-generating rather than hypothesis-based

  • Metabolomics has been used to determine the roles of specific genes in the development of cardiac diseases and to define metabolic phenotypes associated with given genetic modifications

  • Metabolomics has been used in the search for biomarkers for cardiac disorders in humans; however, a novel, validated biomarker for cardiac disease is still being sought

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Figure 1: Metabolomics in the spectrum of functional-genomic approaches, with emphasis on lipidomics.
Figure 2: Metabolomic analysis by chromatography with MS.
Figure 3: Techniques for measuring the components of the lipidome of the heart.
Figure 4: Further characterization of the lipidome by tandem MS.
Figure 5: Using metabolomics to model.
Figure 6: In vivo spectra from the heart of a male Wistar rat.

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Acknowledgements

J. L. Griffin is supported by grants from the Medical Research Council (G0801841), the Biotechnology and Biological Sciences Research Council (BB/H013539/1), European Union Framework 7 (INHERITANCE), and the Wellcome Trust (093,148/Z/10/Z). H. Atherton is supported by the Biotechnology and Biological Sciences Research Council (BB/H013539/1) and the Medical Research Council. The authors thank Dr Damian Tyler, University of Oxford, UK for supplying Figure 6.

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J. L. Griffin, H. Atherton, and J. Shockcor researched the data for the article. J. L. Griffin and L. Atzori discussed the content of the Review, and J. L. Griffin wrote the manuscript. All the authors were involved with reviewing and editing the manuscript before submission.

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Correspondence to Julian L. Griffin.

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Griffin, J., Atherton, H., Shockcor, J. et al. Metabolomics as a tool for cardiac research. Nat Rev Cardiol 8, 630–643 (2011). https://doi.org/10.1038/nrcardio.2011.138

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