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Metabolic adaptation during cardiac exercise rehabilitation in patients after a first myocardial infarction

ABSTRACT: Cardiac rehabilitation (CR) is highly beneficial in post-myocardial infarction (MI) patients; however, its metabolic impact remains underexplored. This study investigated metabolic and lipidomic adaptations to an intensive CR program in 25 non-diabetic male patients (<75 years) following a first uncomplicated ST-elevation MI (STEMI). CR involved 24 +/- 3 sessions, with baseline and final clinical assessments and, in a subgroup of 17 patients, longitudinal dried blood spots (DBS) were collected and metabolomics/lipidomics analysis was also performed. CR significantly improved clinical outcomes, including the 6-minute walk test, B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF%), C-reactive protein (CRP), and homocysteine levels. Metabolomic analysis showed long-term positive adaptations, notably increased N-acetyl-L-tyrosine (NAT), suggesting a mitohormesis response to exercise-induced mitochondrial stress. The third training session exhibited the highest metabolic adaptation, primarily in energy metabolism pathways like the TCA cycle, indicating enhanced oxidative energy generation and improved exercise performance. The lipidome displayed an acute response to the first training, with upregulation of phosphatidylserines (PS). Predicted increased activity of PSS1, enzymes vital for PS synthesis, underscores PS's protective role in myocardial damage and its contribution to muscle activity. These findings highlight CR's beneficial metabolic adaptations, potentially via mitohormesis, and suggest modulating NAT and PS levels could enhance patient recovery and cardiac function.

INSTRUMENT(S): 6545 Q-TOF LC/MS

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Giuseppe Paglia

PROVIDER: MSV000098996 | MassIVE |

REPOSITORIES: MassIVE

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Project description:Purpose: Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and soleus gene expression we examined genome-wide gene expression in soleus muscle of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in man, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in the two groups, since accumulating evidence indicates that exercise has profound beneficial effects on the metabolic syndrome. Methods:; Soleus gene expression of both sedentary and exercise trained HCR and LCR was characterized by microarray- and gene ontology analysis. Results: Although HCR and LCR had an inborn 347% difference in running capacity, only three genes were found differentially expressed in the soleus muscle between the two groups. Up-regulation of the mitochondrial enzyme leucyl-transferRNA synthetase (LARS2) was found in the sedentary LCR. Increased expression of LARS2 has been associated with a mitochondrial DNA mutation linked to maternally inherited diabetes and mitochondrial dysfunction. In line with our findings, a growing body of evidence suggests that LCR have compromised mitochondrial function. After exercise training, 58 genes were altered in the soleus muscle of HCR, in contrast to only one in the LCR group. This suggests that animals born with different levels of fitness respond different to the same type of exercise training. Adaptations to exercise in HCR seemed to be associated with increased lipid metabolism and fatty acid elongation in the mitochondria. Also, genes associated with the peroxisomes, seemed to be central in the adaptation to exercise. Conclusion: The results indicate that (i) LCR might have mitochondrial dysfunction, which may be a contributing factor of the low inborn aerobic capacity, (ii) animals born with different levels of fitness respond different to the same exercise program. Experiment Overall Design: There are 16 samples in this study.

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Metabolic adaptation during cardiac exercise rehabilitation in patients after a first myocardial infarction

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