Skip to main content
SpringerLink
Log in

Metabonomics Study of Heart Homogenates from Myocardial Infarction Rats Using Liquid Chromatography/Time of Flight Mass Spectrometry

  • Original
  • Published:
Chromatographia Aims and scope Submit manuscript

Abstract

In this study, a metabonomics analysis of heart homogenates from myocardial ischemic rats was performed by LC–TOF–MS. Hydrophilic interaction chromatography (HILIC) was used to separate the endogenous metabolites in heart homogenates. Partial least squares to latent structure-discriminant analysis (PLS-DA) was used for data analysis. Good separations were observed between the normal and model groups and 15 potential biomarkers were identified. The major disturbed metabolic pathways were purine metabolism, pyrimidine metabolism, urea cycle, and energy metabolism. The results demonstrated that a metabonomics approach based on HILIC-MS was useful for studying metabolic mechanism on target tissue of the myocardial infarction rat.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Aronow WS (2006) Epidemiology, pathophysiology, prognosis, and treatment of systolic and diastolic heart failure. Cardiol Rev 14:108–124

    Article  Google Scholar 

  2. Sansbury BE, DeMartino AM, Xie Z, Brooks AC, Brainard RE, Watson LJ, DeFilippis AP, Cummins TD, Harbeson MA, Brittian KR et al (2014) Metabolomic analysis of pressure-overloaded and infarcted mouse hearts. Circ Heart Fail 7:634–642

    Article  CAS  Google Scholar 

  3. Spagou K, Wilson ID, Masson P, Theodoridis G, Raikos N, Coen M, Holmes E, Lindon JC, Plumb RS, Nicholson JK, Want EJ (2011) HILIC-UPLC-MS for exploratory urinary metabolic profiling in toxicological studies. Anal Chem 83:382–390

    Article  CAS  Google Scholar 

  4. Cubbon S, Antonio C, Wilson J, Thomas-Oates J (2010) Metabolomic applications of HILIC-LC-MS. Mass Spectrom Rev 29:671–684

    Article  CAS  Google Scholar 

  5. Garcia-Canaveras JC, Donato MT, Castell JV, Lahoz A (2011) A comprehensive untargeted metabonomic analysis of human steatotic liver tissue by RP and HILIC chromatography coupled to mass spectrometry reveals important metabolic alterations. J Proteome Res 10:4825–4834

    Article  CAS  Google Scholar 

  6. Spagou K, Tsoukali H, Raikos N, Gika H, Wilson ID, Theodoridis G (2010) Hydrophilic interaction chromatography coupled to MS for metabonomic/metabolomic studies. J Sep Sci 33:716–727

    Article  CAS  Google Scholar 

  7. Yin P, Wan D, Zhao C, Chen J, Zhao X, Wang W, Lu X, Yang S, Gu J, Xu G (2009) A metabonomic study of hepatitis B-induced liver cirrhosis and hepatocellular carcinoma by using RP-LC and HILIC coupled with mass spectrometry. Mol BioSyst 5:868–876

    Article  CAS  Google Scholar 

  8. Jiang P, Dai W, Yan S, Chen Z, Xu R, Ding J, Xiang L, Wang S, Liu R, Zhang W (2011) Biomarkers in the early period of acute myocardial infarction in rat serum and protective effects of Shexiang Baoxin Pill using a metabolomic method. J Ethnopharmacol 138:530–536

    Article  Google Scholar 

  9. Liu YT, Jia HM, Chang X, Ding G, Zhang HW, Zou ZM (2013) The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics. Mol BioSyst 9:2823–2834

    Article  CAS  Google Scholar 

  10. Tan G, Lou Z, Liao W, Dong X, Zhu Z, Li W, Chai Y (2012) Hydrophilic interaction and reversed-phase ultra performance liquid chromatography TOF–MS for serum metabonomic analysis of myocardial infarction in rats and its applications. Mol BioSyst 8:548–556

    Article  CAS  Google Scholar 

  11. Ciborowski M, Martin-Ventura JL, Meilhac O, Michel JB, Ruperez FJ, Tunon J, Egido J, Barbas C (2011) Metabolites secreted by human atherothrombotic aneurysms revealed through a metabolomic approach. J Proteome Res 10:1374–1382

    Article  CAS  Google Scholar 

  12. Liu SY, Zhang RL, Kang H, Fan ZJ, Du Z (2013) Human liver tissue metabolic profiling research on hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol 19:3423–3432

    Article  CAS  Google Scholar 

  13. Liu YT, Jia HM, Chang X, Ding G, Zhang HW, Zou ZM (2013) The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics. Mol BioSyst 9:2823–2834

    Article  CAS  Google Scholar 

  14. Zhang F, Jia Z, Gao P, Kong H, Li X, Chen J, Yang Q, Yin P, Wang J, Lu X et al (2009) Metabonomics study of atherosclerosis rats by ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry. Talanta 79:836–844

    Article  CAS  Google Scholar 

  15. Tianjiao L, Shuai W, Xiansheng M, Yongrui B, Shanshan G, Bo L, Lu C, Lei W, Xiaorong R (2014) Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in gastric ulcer and intervention effects of Corydalis yanhusuo alkaloid. PLoS One 9:e82499

    Article  Google Scholar 

  16. Zhao L, Wan L, Qiu X, Li R, Liu S, Wang D (2014) A metabonomics profiling study on phlegm syndrome and blood-stasis syndrome in coronary heart disease patients using liquid chromatography/quadrupole time-of-flight mass spectrometry. Evid Based Complement Alternat Med 2014:385102

    Google Scholar 

  17. Farthing DE, Farthing CA, Xi L (2015) Inosine and hypoxanthine as novel biomarkers for cardiac ischemia: from bench to point-of-care. Exp Biol Med (Maywood) 240:821–831

    Article  CAS  Google Scholar 

  18. Berry CE, Hare JM (2004) Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol 555:589–606

    Article  CAS  Google Scholar 

  19. Long Y, Dong X, Yuan Y, Huang J, Song J, Sun Y, Lu Z, Yang L, Yu W (2015) Metabolomics changes in a rat model of obstructive jaundice: mapping to metabolism of amino acids, carbohydrates and lipids as well as oxidative stress. J Clin Biochem Nutr 57:50–59

    Article  CAS  Google Scholar 

  20. Conotte R, Colet JM (2014) A metabonomic evaluation of the monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats. Toxicol Appl Pharmacol 276:147–156

    Article  CAS  Google Scholar 

  21. Jiang P, Dai W, Yan S, Chen Z, Xu R, Ding J, Xiang L, Wang S, Liu R, Zhang W (2011) Potential biomarkers in the urine of myocardial infarction rats: a metabolomic method and its application. Mol BioSyst 7:824–831

    Article  CAS  Google Scholar 

  22. Wu S, Tan G, Dong X, Zhu Z, Li W, Lou Z, Chai Y (2013) Metabolic profiling provides a system understanding of hypothyroidism in rats and its application. PLoS One 8:e55599

    Article  CAS  Google Scholar 

  23. Yaoita H, Fischman AJ, Strauss HW, Saito T, Sato E, Maruyama Y (1993) Uridine: a marker of myocardial viability after coronary occlusion and reperfusion. Int J Card Imaging 9:273–280

    Article  CAS  Google Scholar 

  24. Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336(Pt 1):1–17

    Article  CAS  Google Scholar 

  25. Carnicer R, Crabtree MJ, Sivakumaran V, Casadei B, Kass DA (2013) Nitric oxide synthases in heart failure. Antioxid Redox Signal 18:1078–1099

    Article  CAS  Google Scholar 

  26. Wang Z, Tang WH, Cho L, Brennan DM, Hazen SL (2009) Targeted metabolomic evaluation of arginine methylation and cardiovascular risks: potential mechanisms beyond nitric oxide synthase inhibition. Arterioscler Thromb Vasc Biol 29:1383–1391

    Article  CAS  Google Scholar 

  27. Hu A, Jiao X, Gao E, Koch WJ, Sharifi-Azad S, Grunwald Z, Ma XL, Sun JZ (2006) Chronic beta-adrenergic receptor stimulation induces cardiac apoptosis and aggravates myocardial ischemia/reperfusion injury by provoking inducible nitric-oxide synthase-mediated nitrative stress. J Pharmacol Exp Ther 318:469–475 (Epub 2006 Mar 2030)

    Article  CAS  Google Scholar 

  28. Mungrue IN, Gros R, You X, Pirani A, Azad A, Csont T, Schulz R, Butany J, Stewart DJ, Husain M (2002) Cardiomyocyte overexpression of iNOS in mice results in peroxynitrite generation, heart block, and sudden death. J Clin Invest 109:735–743

    Article  CAS  Google Scholar 

  29. Morris SM Jr (2002) Regulation of enzymes of the urea cycle and arginine metabolism. Annu Rev Nutr 22:87–105

    Article  CAS  Google Scholar 

  30. Ippolito DL, Lewis JA, Yu C, Leon LR, Stallings JD (2014) Alteration in circulating metabolites during and after heat stress in the conscious rat: potential biomarkers of exposure and organ-specific injury. BMC Physiol 14:14

    Article  Google Scholar 

  31. Neill MA, Aschner J, Barr F, Summar ML (2009) Quantitative RT-PCR comparison of the urea and nitric oxide cycle gene transcripts in adult human tissues. Mol Genet Metab 97:121–127

    Article  CAS  Google Scholar 

  32. Baguet A, Reyngoudt H, Pottier A, Everaert I, Callens S, Achten E, Derave W (1985) Carnosine loading and washout in human skeletal muscles. J Appl Physiol 2009(106):837–842

    Google Scholar 

  33. Stvolinsky SL, Dobrota D (2000) Anti-ischemic activity of carnosine. Biochemistry (Mosc) 65:849–855

    CAS  Google Scholar 

Download references

Acknowledgments

The work was supported financially by National Natural Science Foundation of China (nos. 81202950), the National Basic Research Program of China (973 Program, 2015 CB 554400), the National Science and Technology Major Project of China (nos. 2012 ZX 09103201-049).

Author information

Authors and Affiliations

  1. Xiyuan Hospital, China Academy of Chinese Medical Sciences and Beijing Key Lab of TCM Pharmacology, No. 1, Xiyuan Caochang, Haidian District, Beijing, 100091, China

    Mingqian Sun, Lei Sun, Lan Miao, Li Lin, Shuo Huang, Bin Yang, Jianhua Fu, Zhengyan Ge, Long Jin & Jianxun Liu

  2. Beijing University of Chinese Medicine, Beijing, 100029, China

    Lei Sun

Authors
  1. Mingqian Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lan Miao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shuo Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jianhua Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhengyan Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Long Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jianxun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jianxun Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests.

Research involving animals

All animal studies performed in accordance with the Chinese guidelines for the Laboratory Animals Care.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 752 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, M., Sun, L., Miao, L. et al. Metabonomics Study of Heart Homogenates from Myocardial Infarction Rats Using Liquid Chromatography/Time of Flight Mass Spectrometry. Chromatographia 79, 1309–1316 (2016). https://doi.org/10.1007/s10337-016-3136-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10337-016-3136-7

Keywords

Search

Navigation