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STATE-OF-THE-ART PAPER

Application of Metabolomics to Cardiovascular Biomarker and Pathway Discovery

Gregory D. Lewis, MD^_*,,, Aarti Asnani, BS^_*, and Robert E. Gerszten, MD^_*,,,_*

^_* Center for Immunology and Inflammatory Diseases and Cardiology Division, Massachusetts General Hospital, Charlestown, Massachusetts
Center for Immunology and Inflammatory Diseases and Cardiology Division, Harvard Medical School, Boston, Massachusetts
Broad Institute of MIT and Harvard, Cambridge, Massachusetts.

Manuscript received May 30, 2007; revised manuscript received February 22, 2008, accepted March 24, 2008.

^_* Reprint requests and correspondence: Dr. Robert E. Gerszten, Cardiology Division and Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital East-8307, 149 13th Street, Charlestown, Massachusetts 02129. (Email: rgerszten{at}partners.org).

Emerging technologies based on mass spectrometry and nuclear magnetic resonance enable the monitoring of hundreds of metabolites from tissues or body fluids, that is, "metabolomics." Because metabolites change rapidly in response to physiologic perturbations, they represent proximal reporters of disease phenotypes. The profiling of low molecular weight biochemicals, including lipids, sugars, nucleotides, organic acids, and amino acids, that serve as substrates and products in metabolic pathways is particularly relevant to cardiovascular diseases. In addition to serving as disease biomarkers, circulating metabolites may participate in previously unanticipated roles as regulatory signals with hormone-like functions. Cellular metabolic pathways are highly conserved among species, facilitating complementary functional studies in model organisms to provide insight into metabolic changes identified in humans. Although metabolic profiling technologies and methods of pattern recognition and data reduction remain under development, the coupling of metabolomics with other functional genomic approaches promises to extend our ability to elucidate biological pathways and discover biomarkers of human disease.

Key Words: metabolomics • biomarkers • prognosis

Abbreviations and Acronyms   GC = gas chromatography   LC = liquid chromatography   MS = mass spectrometry   NMR = nuclear magnetic resonance   TCA = tricarboxylic acid