Metabolic disorder in the progression of heart failure
- 5 Downloads
Heart failure (HF) is a major clinical concern owing to its high prevalence and high mortality. Metabolomics, an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathogenesis, has been extensively applied in evaluating the course of diseases. In this study, we used this approach to analyse the abundance of metabolites, with liquid chromatograph-mass spectrometer, in plasma samples from rats with transverse aortic constriction (TAC) and patients at different stages of HF. We compared the metabolic parameters within and between TAC rats and patients. An apparent metabolic shift was observed in rats, from compensated hypertrophy stage to decompensated hypertrophy stage, and in patients with HF, from stage A to stage B and subsequently stage C. Diagnostic biomarkers were predicted by comparing the variable importance in the projection scores and fold change analysis within and between rats and patients. Enrichment pathway analysis and network analysis provided an overview of the largely disturbed metabolic pathways, and those interfered at different stages and across species were confirmed. The significantly changed metabolites and pathways revealed the underlying mechanisms of HF pathogenesis, hinted at novel potential biomarkers, and provided potential therapeutic intervention targets for HF.
Keywordsheart failure metabolomics TAC HF stages A–C biomarker pathway analysis
Unable to display preview. Download preview PDF.
This work was supported by the National Natural Science Foundation of China (81625001, 81700010) and National Key Research & Development Program of China (2018YFC1312700, 2018YFC1312701).
- Berger, R., Moertl, D., Peter, S., Ahmadi, R., Huelsmann, M., Yamuti, S., Wagner, B., and Pacher, R. (2010). N-terminal pro-B-type natriuretic peptide-guided, intensive patient management in addition to multidisciplinary care in chronic heart failure. J Am Coll Cardiol 55, 645–653.CrossRefGoogle Scholar
- Dunn, W.B., Broadhurst, D.I., Deepak, S.M., Buch, M.H., McDowell, G., Spasic, I., Ellis, D.I., Brooks, N., Kell, D.B., and Neyses, L. (2007). Serum metabolomics reveals many novel metabolic markers of heart failure, including pseudouridine and 2-oxoglutarate. Metabolomics 3, 413–426.CrossRefGoogle Scholar
- Hunt, S.A., Abraham, W.T., Chin, M.H., Feldman, A.M., Francis, G.S., Ganiats, T.G., Jessup, M., Konstam, M.A., Mancini, D.M., Michl, K., et al. (2009). 2009 focused update incorporated into the acc/aha 2005 guidelines for the diagnosis and management of heart failure in adults. Circulation 119.Google Scholar
- Maisel, A.S., Clopton, P., Krishnaswamy, P., Nowak, R.M., McCord, J., Hollander, J.E., Duc, P., Omland, T., Storrow, A.B., Abraham, W.T., et al. (2004). Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing Not Properly (BNP) multinational study. Am Heart J 147, 1078–1084.CrossRefGoogle Scholar
- Mueller-Hennessen, M., Sigl, J., Fuhrmann, J.C., Witt, H., Reszka, R., Schmitz, O., Kastler, J., Fischer, J.J., Müller, O.J., Giannitsis, E., et al. (2017). Metabolic profiles in heart failure due to non-ischemic cardiomyopathy at rest and under exercise. ESC Heart Fail 4, 178–189.CrossRefGoogle Scholar
- Schneider, A., Markowski, A., Momma, M., Seipt, C., Luettig, B., Hadem, J., Wilhelmi, M., Manns, M.P., and Wedemeyer, J. (2011). Tolerability and efficacy of a low-volume enteral supplement containing key nutrients in the critically ill. Clrin Nutrit 30, 599–603.Google Scholar
- Senthong, V., Li, X.S., Hudec, T., Coughlin, J., Wu, Y., Levison, B., Wang, Z., Hazen, S.L., and Tang, W.H.W. (2016). Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with atherosclerotic burden. J Am Coll Cardiol 67, 2620–2628.CrossRefGoogle Scholar
- Shao, M., Huang, C., Li, Z., Yang, H., and Feng, Q. (2014). Effects of glutamine and valsartan on the brain natriuretic peptide and n-terminal pro-b-type natriuretic peptide of patients with chronic heart failure. Pak J Med Sci 31.Google Scholar
- Tang, W.H.W., Wang, Z., Shrestha, K., Borowski, A.G., Wu, Y., Troughton, R.W., Klein, A.L., and Hazen, S.L. (2015). Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure. J Cardiac Fail 21, 91–96.CrossRefGoogle Scholar