https://orcid.org/0000-0001-6877-0288
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Silvia G Priori, Andrea Mazzanti, Warning: not all carriers of pathogenic mutations in desmosomal genes should follow the same medical advices!, Cardiovascular Research, Volume 116, Issue 6, 1 May 2020, Pages 1085–1088, https://doi.org/10.1093/cvr/cvaa049
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This editorial refers to ‘Exercise restores dysregulated gene expression in a mouse model of arrhythmogenic cardiomyopathy’, by S.M. Cheedipudi et al., pp. 1199–1213.
The study by Cheedipudi et al.1 published in this issue of the Journal provides very provocative and thought-generating data that highlight the existence of a major adaptive response of the murine heart to environmental stressors and particularly to exercise.
The team of authors led by Dr Marian have provided in the past enlightening contributions to the understanding of the pathogenesis of the arrhythmogenic cardiomyopathy (ACM)2–4 and in this investigation, they explore the interesting question of whether physical training may impact cardiac transcriptomic in wild-type mice and in ACM mice.
The first novel contribution provided by the study comes from the idea of assessing transcriptional changes in cardiac cells of wild-type mice exposed to regular physical exercise up to 6 months of age and showing that physical training triggers transcriptional changes in healthy animals. Despite it is well known that cardiac remodelling occurs in athletes, the underlying molecular mechanisms are largely undefined as data on exercise-related transcriptional changes in cardiac cells in humans are missing. The study by Cheedipudi et al.1 nicely demonstrates that, at least in young rodents, physical training modifies the transcriptome and pinpoints to some pathways that are modulated. Overall, the authors report changes in transcript levels of 2529 genes in wild-type mice, of which 1390 are up-regulated and 1139 down-regulated. Looking at the pathways implicated in this process, the authors noted the up-regulation of genes that regulate protein secretion, mitotic spindle, and PI3K/AKT/mTOR signalling. Interestingly, down-regulated genes were involved in inflammation and oxidative phosphorylation. These observations are most valuable, as they may guide human studies to better define the mechanisms for the health promoting role of exercise in athletes and in the population with an active lifestyle.
