Disturbed energy and amino acid metabolism with their diagnostic potential in mitral valve disease revealed by untargeted plasma metabolic profiling
Mitral valve disease (MVD), including mitral valve regurgitation (MR) and mitral valve stenosis (MS), is a chronic and progressive cardiac malady. However, the metabolic alterations in MVD is not well-understood till now. The current gold standard diagnostic test, transthoracic echocardiography, has limitations on high-throughput measurement and lacks molecular information for early diagnosis of the disease.
The present study aimed to investigate the biochemical alterations and to explore their diagnostic potential for MVD.
Plasma metabolic profile derangements and their diagnostic potential were non-invasively explored in 34 MR and 20 MS patients against their corresponding controls, using high-throughput NMR-based untargeted metabolomics.
Eighteen differential metabolites were identified for MR and MS patients respectively, on the basis of multivariate and univariate data analysis, which were mainly involved in energy metabolism, amino acid metabolism, calcium metabolism and inflammation. These differential metabolites, notably the significantly down-regulated formate and lactate, showed high diagnostic potential for MVD by using Spearman’s rank-order correlation analysis and ROC analysis.
To the best of our knowledge, the present study is the first one that explores the metabolic derangements and their diagnostic values in MVD patients using metabolomics. The findings indicated that metabolic disturbance occurred in MVD patients, with plasma formate and lactate emerged as important candidate biomarkers for MVD.
KeywordsMitral valve regurgitation Mitral valve stenosis Metabolomics NMR Formate Lactate
The authors gratefully acknowledge the participation of all patients and healthy controls. The authors thank Professor An Pan (HUST) for his valuable comments and constructive suggestions. The authors gratefully acknowledge Dr Junfang Wu for the kind help on language editing during manuscript revision.
LJ, DSJ, ZMF, XHZ and XW designed the study. JW, RL, HWL and XY collected samples. LJ conduced the NMR experiment and analyzed the metabolomics data. LJ, JW, RL, HWL and XY analyzed the data. LJ, JW, and DSJ wrote the manuscript. LJ, JW, DSJ, ZMF, XHZ and XW revised the manuscript.
This work was supported by Grants from the National Natural Science Foundation of China (Nos. 81600188, 81670050), the Natural Science Foundation of Hubei Province (No. 2016CFB162), the Tongji Hospital Fund for Distinguished Young Scholars (No. 2016YQ02), Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, Huazhong University of Science and Technology, and the start-up grant from Huazhong University of Science and Technology (513-3004513113).
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
All procedures performed in this study were in accordance with the ethical standards of the ethics committee of Tongji Hospital, Huazhong University of Science and Technology (HUST) and with the 1964 Helsinki declaration and its later amendments. Informed consent was obtained from all individual participants included in the study.
- Baumgartner, H., Falk, V., Bax, J. J., De Bonis, M., Hamm, C., Holm, P. J., et al. (2017). 2017 ESC/EACTS guidelines for the management of valvular heart disease the task force for the management of valvular heart disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). European Heart Journal, 38, 2739–2791.CrossRefGoogle Scholar
- Cheng, M. L., Wang, C. H., Shiao, M. S., Liu, M. H., Huang, Y. Y., Huang, C. Y., et al. (2015). Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure diagnostic and prognostic value of metabolomics. Journal of the American College of Cardiology, 65, 1509–1520.CrossRefGoogle Scholar
- Duprez, D. A., Otvos, J., Sanchez, O. A., Mackey, R. H., Tracy, R., & Jacobs, D. R. (2016). Comparison of the predictive value of glyca and other biomarkers of inflammation for total death, incident cardiovascular events, noncardiovascular and noncancer inflammatory-related events, and total cancer events. Clinical Chemistry, 62, 1020–1031.CrossRefGoogle Scholar
- Gregory, J. F., Cuskelly, G. J., Shane, B., Toth, J. P., Baumgartner, T. G., & Stacpoole, P. W. (2000). Primed, constant infusion with [2H3]serine allows in vivo kinetic measurement of serine turnover, homocysteine remethylation, and transsulfuration processes in human one-carbon metabolism. American Journal of Clinical Nutrition, 72, 1535–1541.CrossRefGoogle Scholar
- Li, Q. H., Freeman, L. M., Rush, J. E., Huggins, G. S., Kennedy, A. D., Labuda, J. A., et al. (2015). Veterinary medicine and multi-omics research for future nutrition targets: Metabolomics and transcriptomics of the common degenerative mitral valve disease in dogs. Omics: A Journal of Integrative Biology, 19, 461–470.CrossRefGoogle Scholar
- Mourino-Alvarez, L., Baldan-Martin, M., Gonzalez-Calero, L., Martinez-Laborde, C., Sastre-Oliva, T., Moreno-Luna, R., et al. (2016). Patients with calcific aortic stenosis exhibit systemic molecular evidence of ischemia, enhanced coagulation, oxidative stress and impaired cholesterol transport. International Journal of Cardiology, 225, 99–106.CrossRefGoogle Scholar
- Olkowicz, M., Debski, J., Jablonska, P., Dadlez, M., & Smolenski, R. T. (2017). Application of a new procedure for liquid chromatography/mass spectrometry profiling of plasma amino acid-related metabolites and untargeted shotgun proteomics to identify mechanisms and biomarkers of calcific aortic stenosis. Journal of Chromatography A, 1517, 66–78.CrossRefGoogle Scholar
- van Beynum, I. M., Kapusta, L., Bakker, M. K., den Heijer, M., Blom, H. J., & de Walle, H. E. K. (2010). Protective effect of periconceptional folic acid supplements on the risk of congenital heart defects: A registry-based case-control study in the northern Netherlands. European Heart Journal, 31, 464–471.CrossRefGoogle Scholar