Difference in Metabolomic Response to Exercise between Patients with and without Hypertrophic Cardiomyopathy
Yuichi J Shimada1,2, Jaya Batra3, Stephanie M Kochav3
1Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA. ys3053@cumc.columbia.edu.
Insights
Hypertrophic cardiomyopathy (HCM) does not alter cardiac metabolism at rest. Exercise reveals significant metabolic pathway differences in HCM patients, impacting aminoacyl-tRNA biosynthesis and nitrogen metabolism.
Area of Science:
- Cardiology
- Metabolomics
- Biochemistry
Background:
- Hypertrophic cardiomyopathy (HCM) is a complex cardiac condition.
- The impact of HCM on cardiac metabolic pathways during physiological stress remains poorly understood.
Purpose of the Study:
- To investigate the effects of hypertrophic cardiomyopathy on cardiac metabolic pathways at rest and during exercise.
- To identify specific metabolic pathways dysregulated in HCM patients under exercise stress.
Main Methods:
- A case-control study involving 15 HCM patients and 2 control groups.
- Comprehensive metabolomic profiling of 210 metabolites at rest and peak exercise.
- Statistical analysis including partial least squares discriminant analysis and pathway enrichment analysis.
Main Results:
- No significant differences in metabolomic profiles were observed between HCM cases and controls at rest.
- Significant exercise-induced alterations in metabolomic profiles were detected in HCM patients (p < 0.05).
- Affected pathways include aminoacyl-tRNA biosynthesis, nitrogen metabolism, glycine/serine/threonine metabolism, and arginine/proline metabolism.
Conclusions:
- Hypertrophic cardiomyopathy does not significantly alter cardiac metabolism at rest.
- Exercise stress unmasks significant differential regulation of key metabolic pathways in HCM patients.
- These findings highlight exercise-induced metabolic disturbances as a potential factor in HCM pathophysiology.
Abstract:
It is unclear how hypertrophic cardiomyopathy (HCM) affects cardiac metabolic pathways at rest and with exercise. This case-control study compared 15 cases with HCM to 2 control groups without HCM. Metabolomic profiling of 210 metabolites was carried out at rest and at peak exercise. The 50 most discriminant metabolites differentially regulated during exercise were selected using partial least squares discriminant analysis. Pathway enrichment analysis was also performed. At rest, no significant difference was observed in metabolomic profiling of HCM cases as compared to controls. By contrast, there were significant differences in metabolomic profiling in response to exercise (p < 0.05) in the following metabolic pathways: the aminoacyl-tRNA biosynthesis pathway; the nitrogen metabolism pathway; the glycine, serine, and threonine metabolism pathway; and the arginine and proline metabolism pathway. The present study demonstrates differential regulation of several metabolic pathways in patients with HCM in the setting of exercise stress.
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