5.9
CiteScore
5.9
Impact Factor
Volume 44 Issue 3
Mar.  2017
Turn off MathJax
Article Contents

Metabolomics through the lens of precision cardiovascular medicine

doi: 10.1016/j.jgg.2017.02.004
More Information
  • Corresponding author: E-mail address: ghshui@genetics.ac.cn (Guanghou Shui)
  • Received Date: 2017-01-25
  • Accepted Date: 2017-02-27
  • Rev Recd Date: 2017-02-21
  • Available Online: 2017-03-08
  • Publish Date: 2017-03-20
  • Metabolomics, which targets at the extensive characterization and quantitation of global metabolites from both endogenous and exogenous sources, has emerged as a novel technological avenue to advance the field of precision medicine principally driven by genomics-oriented approaches. In particular, metabolomics has revealed the cardinal roles that the environment exerts in driving the progression of major diseases threatening public health. Herein, the existent and potential applications of metabolomics in two key areas of precision cardiovascular medicine will be critically discussed: 1) the use of metabolomics in unveiling novel disease biomarkers and pathological pathways; 2) the contribution of metabolomics in cardiovascular drug development. Major issues concerning the statistical handling of big data generated by metabolomics, as well as its interpretation, will be briefly addressed. Finally, the need for integration of various omics branches and adopting a multi-omics approach to precision medicine will be discussed.
  • loading
  • [1]
    Alexander, D., Lombardi, R., Rodriguez, G. et al. Metabolomic distinction and insights into the pathogenesis of human primary dilated cardiomyopathy Eur. J. Clin. Invest., 41 (2011),pp. 527-538
    [2]
    Aronson, S.J., Rehm, H.L. Building the foundation for genomics in precision medicine Nature, 526 (2015),pp. 336-342
    [3]
    Arumugam, M., Raes, J., Pelletier, E. et al. Enterotypes of the human gut microbiome Nature, 473 (2011),pp. 174-180
    [4]
    Athey, B.D., Braxenthaler, M., Haas, M. et al. tranSMART: an open source and community-driven informatics and data sharing platform for clinical and translational research AMIA Jt. Summits Transl. Sci. Proc., 2013 (2013),pp. 6-8
    [5]
    Baig, F., Pechlaner, R., Mayr, M. Caveats of untargeted metabolomics for biomarker discovery J. Am. Coll. Cardiol., 68 (2016),pp. 1294-1296
    [6]
    Becker, S., Kortz, L., Helmschrodt, C. et al. LC–MS-based metabolomics in the clinical laboratory J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 883–884 (2012),pp. 68-75
    [7]
    Brown, J.M., Hazen, S.L. Metaorganismal nutrient metabolism as a basis of cardiovascular disease Curr. Opin. Lipidol., 25 (2014),pp. 48-53
    [8]
    Brown, J.M., Hazen, S.L. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases Annu. Rev. Med., 66 (2015),pp. 343-359
    [9]
    Charach, G., Grosskopf, I., Rabinovich, A. et al. The association of bile acid excretion and atherosclerotic coronary artery disease Ther. Adv. Gastroenterol., 4 (2011),pp. 95-101
    [10]
    Charach, G., Rabinovich, A., Argov, O. et al. The role of bile acid excretion in atherosclerotic coronary artery disease Int. J. Vasc. Med., 2012 (2012),p. 949672
    [11]
    Chen, X., Liu, L., Palacios, G. et al. Plasma metabolomics reveals biomarkers of the atherosclerosis J. Sep. Sci., 33 (2010),pp. 2776-2783
    [12]
    Cheng, M.L., Wang, C.H., Shiao, M.S. et al. Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics J. Am. Coll. Cardiol., 65 (2015),pp. 1509-1520
    [13]
    Ciborowski, M., Martin-Ventura, J.L., Meilhac, O. et al. Metabolites secreted by human atherothrombotic aneurysms revealed through a metabolomic approach J. Proteome Res., 10 (2011),pp. 1374-1382
    [14]
    Collins, F.S., Varmus, H. A new initiative on precision medicine New Engl. J. Med., 372 (2015),pp. 793-795
    [15]
    Consortium, C.A.D., Deloukas, P., Kanoni, S. et al. Large-scale association analysis identifies new risk loci for coronary artery disease Nat. Genet., 45 (2013),pp. 25-33
    [16]
    de Couto, G., Ouzounian, M., Liu, P.P. Early detection of myocardial dysfunction and heart failure Nat. Rev. Cardiol., 7 (2010),pp. 334-344
    [17]
    Demirkan, A., van Duijn, C.M., Ugocsai, P. et al. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations PLoS Genet., 8 (2012),p. e1002490
    [18]
    Dunn, W.B., Broadhurst, D.I., Deepak, S.M. et al. Serum metabolomics reveals many novel metabolic markers of heart failure, including pseudouridine and 2-oxoglutarate Metabolomics, 3 (2007),pp. 413-426
    [19]
    Ellero-Simatos, S., Lewis, J.P., Georgiades, A. et al. Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability CPT Pharm. Syst. Pharmacol., 3 (2014),p. e125
    [20]
    Fan, Y., Li, Y., Chen, Y. et al. Comprehensive metabolomic characterization of coronary artery diseases J. Am. Coll. Cardiol., 68 (2016),pp. 1281-1293
    [21]
    Golledge, J., Tsao, P.S., Dalman, R.L. et al. Circulating markers of abdominal aortic aneurysm presence and progression Circulation, 118 (2008),pp. 2382-2392
    [22]
    Griffin, J.L., Atherton, H., Shockcor, J. et al. Metabolomics as a tool for cardiac research Nat. Rev. Cardiol., 8 (2011),pp. 630-643
    [23]
    Hicks, A.A., Pramstaller, P.P., Johansson, A. et al. Genetic determinants of circulating sphingolipid concentrations in European populations PLoS Genet., 5 (2009),p. e1000672
    [24]
    Hutchins, P.M., Moore, E.E., Murphy, R.C. Electrospray MS/MS reveals extensive and nonspecific oxidation of cholesterol esters in human peripheral vascular lesions J. Lipid Res., 52 (2011),pp. 2070-2083
    [25]
    Jameson, J.L., Longo, D.L. Precision medicine–personalized, problematic, and promising N. Engl. J. Med., 372 (2015),pp. 2229-2234
    [26]
    Kantor, P.F., Lucien, A., Kozak, R. et al. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase Circ. Res., 86 (2000),pp. 580-588
    [27]
    Koeth, R.A., Wang, Z., Levison, B.S. et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis Nat. Med., 19 (2013),pp. 576-585
    [28]
    Korman, A., Oh, A., Raskind, A. et al. Statistical methods in metabolomics Methods Mol. Biol., 856 (2012),pp. 381-413
    [29]
    Krauss, R.M., Zhu, H., Kaddurah-Daouk, R. Pharmacometabolomics of statin response Clin. Pharmacol. Ther., 94 (2013),pp. 562-565
    [30]
    Lam, S.M., Chua, G.H., Li, X.J. et al. Oncotarget, 7 (2016),pp. 55970-55989
    [31]
    Lam, S.M., Shui, G. Lipidomics as a principal tool for advancing biomedical research J. Genet. Genomics, 40 (2013),pp. 375-390
    [32]
    Lam, S.M., Tian, H., Shui, G. Lipidomics, en route to accurate quantitation Biochim. Biophys. Acta (2017)
    [33]
    Lam, S.M., Tong, L., Duan, X. et al. Extensive characterization of human tear fluid collected using different techniques unravels the presence of novel lipid amphiphiles J. Lipid Res., 55 (2014),pp. 289-298
    [34]
    Lam, S.M., Wang, Y., Duan, X. et al. Brain lipidomes of subcortical ischemic vascular dementia and mixed dementia Neurobiol. Aging, 35 (2014),pp. 2369-2381
    [35]
    Lavi, S., McConnell, J.P., Rihal, C.S. et al. Local production of lipoprotein-associated phospholipase A2 and lysophosphatidylcholine in the coronary circulation: association with early coronary atherosclerosis and endothelial dysfunction in humans Circulation, 115 (2007),pp. 2715-2721
    [36]
    Li, N., Liu, J.Y., Qiu, H. et al. Use of metabolomic profiling in the study of arachidonic acid metabolism in cardiovascular disease Congest. Heart Fail., 17 (2011),pp. 42-46
    [37]
    Li, N., Liu, J.Y., Timofeyev, V. et al. Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: Insight gained using metabolomic approaches J. Mol. Cell. Cardiol., 47 (2009),pp. 835-845
    [38]
    Lin, H., Zhang, J., Gao, P. Silent myocardial ischemia is associated with altered plasma phospholipids J. Clin. Lab. Anal., 23 (2009),pp. 45-50
    [39]
    Liu, J.Y., Li, N., Yang, J. et al. Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events Proc. Natl. Acad. Sci. U. S. A., 107 (2010),pp. 17017-17022
    [40]
    Lu, X., Wang, L., Chen, S. et al. Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease Nat. Genet., 44 (2012),pp. 890-894
    [41]
    Lu, Y., Feskens, E.J., Boer, J.M. et al. The potential influence of genetic variants in genes along bile acid and bile metabolic pathway on blood cholesterol levels in the population Atherosclerosis, 210 (2010),pp. 14-27
    [42]
    Mas, S., Martinez-Pinna, R., Martin-Ventura, J.L. et al. Local non-esterified fatty acids correlate with inflammation in atheroma plaques of patients with type 2 diabetes Diabetes, 59 (2010),pp. 1292-1301
    [43]
    Meikle, P.J., Wong, G., Tsorotes, D. et al. Plasma lipidomic analysis of stable and unstable coronary artery disease Arterioscler. Thromb. Vasc. Biol., 31 (2011),pp. 2723-2732
    [44]
    Millington, D.S., Stevens, R.D. Acylcarnitines: analysis in plasma and whole blood using tandem mass spectrometry Methods Mol. Biol., 708 (2011),pp. 55-72
    [45]
    Oni-Orisan, A., Edin, M.L., Lee, J.A. et al. Cytochrome P450-derived epoxyeicosatrienoic acids and coronary artery disease in humans: a targeted metabolomics study J. Lipid Res., 57 (2016),pp. 109-119
    [46]
    Podrez, E.A., Poliakov, E., Shen, Z. et al. Identification of a novel family of oxidized phospholipids that serve as ligands for the macrophage scavenger receptor CD36 J. Biol. Chem., 277 (2002),pp. 38503-38516
    [47]
    Pols, T.W., Nomura, M., Harach, T. et al. TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading Cell Metab., 14 (2011),pp. 747-757
    [48]
    Qin, J., Li, R., Raes, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing Nature, 464 (2010),pp. 59-65
    [49]
    Rajaratnam, R.A., Gylling, H., Miettinen, T.A. Cholesterol absorption, synthesis, and fecal output in postmenopausal women with and without coronary artery disease Arterioscler. Thromb. Vasc. Biol., 21 (2001),pp. 1650-1655
    [50]
    Rasmiena, A.A., Ng, T.W., Meikle, P.J. Metabolomics and ischaemic heart disease Clin. Sci., 124 (2013),pp. 289-306
    [51]
    Relling, M.V., Evans, W.E. Pharmacogenomics in the clinic Nature, 526 (2015),pp. 343-350
    [52]
    Repa, J.J., Mangelsdorf, D.J. The role of orphan nuclear receptors in the regulation of cholesterol homeostasis Annu. Rev. Cell Dev. Biol., 16 (2000),pp. 459-481
    [53]
    Rhee, E.P., Gerszten, R.E. Metabolomics and cardiovascular biomarker discovery Clin. Chem., 58 (2012),pp. 139-147
    [54]
    Sabatine, M.S., Liu, E., Morrow, D.A. et al. Metabolomic identification of novel biomarkers of myocardial ischemia Circulation, 112 (2005),pp. 3868-3875
    [55]
    Salonen, J.T., Nyyssonen, K., Salonen, R. et al. Lipoprotein oxidation and progression of carotid atherosclerosis Circulation, 95 (1997),pp. 840-845
    [56]
    Scheufele, E., Aronzon, D., Coopersmith, R. et al. tranSMART: an open source knowledge management and high content data analytics platform AMIA Jt. Summits Transl. Sci. Proc., 2014 (2014),pp. 96-101
    [57]
    Shah, S.H., Sun, J.L., Stevens, R.D. et al. Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease Am. Heart J., 163 (2012),pp. 844-850
    [58]
    Shui, G., Stebbins, J.W., Lam, B.D. et al. Comparative plasma lipidome between human and cynomolgus monkey: are plasma polar lipids good biomarkers for diabetic monkeys? PLoS One, 6 (2011),p. e19731
    [59]
    Shui, G.H., Lam, S.M., Stebbins, J. et al. Polar lipid derangements in type 2 diabetes mellitus: potential pathological relevance of fatty acyl heterogeneity in sphingolipids Metabolomics, 9 (2013),pp. 786-799
    [60]
    Stanley WC, L.G., Hall, J.L., McCormack, J.G. Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions. Potential for pharmacological interventions Cardiovasc. Res., 33 (1997),p. 14
    [61]
    Stegemann, C., Drozdov, I., Shalhoub, J. et al. Comparative lipidomics profiling of human atherosclerotic plaques Circ. Cardiovasc. Genet., 4 (2011),pp. 232-242
    [62]
    Stewart, N.A., Buch, S.C., Conrads, T.P. et al. A UPLC-MS/MS assay of the “Pittsburgh cocktail”: six CYP probe-drug/metabolites from human plasma and urine using stable isotope dilution Analyst, 136 (2011),pp. 605-612
    [63]
    Storey, J.D., Tibshirani, R. Statistical significance for genomewide studies Proc. Natl. Acad. Sci. U. S. A., 100 (2003),pp. 9440-9445
    [64]
    Sugimoto, M., Kawakami, M., Robert, M. et al. Bioinformatics tools for mass spectroscopy-based metabolomic data processing and analysis Curr. Bioinform., 7 (2012),pp. 96-108
    [65]
    Sun, L., Zhang, X., He, L. GWAS promotes precision medicine in China J. Genet. Genomics, 43 (2016),pp. 477-479
    [66]
    Thukkani, A.K., McHowat, J., Hsu, F.F. et al. Identification of alpha-chloro fatty aldehydes and unsaturated lysophosphatidylcholine molecular species in human atherosclerotic lesions Circulation, 108 (2003),pp. 3128-3133
    [67]
    Tian, H., Lam, S.M., Shui, G. Metabolomics, a powerful tool for agricultural research Int. J. Mol. Sci., 17 (2016)
    [68]
    Turer, A.T., Stevens, R.D., Bain, J.R. et al. Metabolomic profiling reveals distinct patterns of myocardial substrate use in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia/reperfusion Circulation, 119 (2009),pp. 1736-1746
    [69]
    Voora, D., Shah, S.H. Pharmacometabolomics meets genetics: a “natural” clinical trial of statin effects J. Am. Coll. Cardiol., 67 (2016),pp. 1211-1213
    [70]
    Wang, F., Xu, C.Q., He, Q. et al. Genome-wide association identifies a susceptibility locus for coronary artery disease in the Chinese Han population Nat. Genet., 43 (2011),pp. 345-349
    [71]
    Wang, Z., Klipfell, E., Bennett, B.J. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease Nature, 472 (2011),pp. 57-63
    [72]
    Wang, Z., Tang, W.H., Buffa, J.A. et al. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide Eur. Heart J., 35 (2014),pp. 904-910
    [73]
    Winter, G., Kromer, J.O. Fluxomics–connecting 'omics analysis and phenotypes Environ. Microbiol., 15 (2013),pp. 1901-1916
    [74]
    Wishart, D.S. Emerging applications of metabolomics in drug discovery and precision medicine Nat. Rev. Drug Discov., 15 (2016),pp. 473-484
    [75]
    Wurtz, P., Wang, Q., Soininen, P. et al. Metabolomic profiling of statin use and genetic inhibition of HMG-CoA reductase J. Am. Coll. Cardiol., 67 (2016),pp. 1200-1210
    [76]
    Xu, D., Li, N., He, Y. et al. Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors Proc. Natl. Acad. Sci. U. S. A., 103 (2006),pp. 18733-18738
    [77]
    Yan, J., Young, M.E., Cui, L. et al. Increased glucose uptake and oxidation in mouse hearts prevent high fatty acid oxidation but cause cardiac dysfunction in diet-induced obesity Circulation, 119 (2009),pp. 2818-2828
    [78]
    Yang, Z.J., Liu, J., Ge, J.P. et al. Prevalence of cardiovascular disease risk factor in the Chinese population: the 2007‒2008 China National diabetes and metabolic disorders study Eur. Heart J., 33 (2012),pp. 213-220
    [79]
    Yao, X., Sa, R., Ye, C. et al. Effects of thyroid hormone status on metabolic pathways of arachidonic acid in mice and humans: a targeted metabolomic approach Prostagl. Other Lipid Mediat., 118–119 (2015),pp. 11-18
    [80]
    Zhang, X., Yang, N., Ai, D. et al. Systematic metabolomic analysis of eicosanoids after omega-3 polyunsaturated fatty acid supplementation by a highly specific liquid chromatography-tandem mass spectrometry-based method J. Proteome Res., 14 (2015),pp. 1843-1853
    [81]
    Zhang, X., Zhang, D., Jia, H. et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment Nat. Med., 21 (2015),pp. 895-905
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (104) PDF downloads (1) Cited by ()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return