Díaz, M. L., Burgess, K., Burchmore, R. , Gómez, M. A., Gómez-Ochoa, S. A., Echeverría, L. E., Morillo, C. and González, C. I. (2022) Metabolomic profiling of end-stage heart failure secondary to chronic Chagas cardiomyopathy. International Journal of Molecular Sciences, 23(18), 10456. (doi: 10.3390/ijms231810456) (PMID:36142367) (PMCID:PMC9499603)
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Abstract
Chronic Chagas cardiomyopathy (CCC) is the most frequent and severe clinical form of chronic Chagas disease, representing one of the leading causes of morbidity and mortality in Latin America, and a growing global public health problem. There is currently no approved treatment for CCC; however, omics technologies have enabled significant progress to be made in the search for new therapeutic targets. The metabolic alterations associated with pathogenic mechanisms of CCC and their relationship to cellular and immunopathogenic processes in cardiac tissue remain largely unknown. This exploratory study aimed to evaluate the potential underlying pathogenic mechanisms in the failing myocardium of patients with end-stage heart failure (ESHF) secondary to CCC by applying an untargeted metabolomic profiling approach. Cardiac tissue samples from the left ventricle of patients with ESHF of CCC etiology (n = 7) and healthy donors (n = 7) were analyzed using liquid chromatography-mass spectrometry. Metabolite profiles showed altered branched-chain amino acid and acylcarnitine levels, decreased fatty acid uptake and oxidation, increased activity of the pentose phosphate pathway, dysregulation of the TCA cycle, and alterations in critical cellular antioxidant systems. These findings suggest processes of energy deficit, alterations in substrate availability, and enhanced production of reactive oxygen species in the affected myocardium. This profile potentially contributes to the development and maintenance of a chronic inflammatory state that leads to progression and severity of CCC. Further studies involving larger sample sizes and comparisons with heart failure patients without CCC are needed to validate these results, opening an avenue to investigate new therapeutic approaches for the treatment and prevention of progression of this unique and severe cardiomyopathy.
| Item Type: | Articles |
|---|---|
| Additional Information: | This research was funded by the Newton-Caldas Fund (Grant No. 172715657) of the British Council “Linking the power of omic technologies to translational research on neglected tropical diseases” and COLCIENCIAS No 110256934230. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Burgess, Dr Karl and Burchmore, Dr Richard |
| Creator Roles: | Burgess, K.Data curation, Investigation, Writing – review and editing Burchmore, R.Conceptualization, Funding acquisition, Investigation, Project administration, Resources, Writing – review and editing |
| Authors: | Díaz, M. L., Burgess, K., Burchmore, R., Gómez, M. A., Gómez-Ochoa, S. A., Echeverría, L. E., Morillo, C., and González, C. I. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | International Journal of Molecular Sciences |
| Publisher: | MDPI |
| ISSN: | 1661-6596 |
| ISSN (Online): | 1422-0067 |
| Published Online: | 09 September 2022 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in International Journal of Molecular Sciences 23(18): 10456 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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