Abstract
Regular physical activity with aerobic and muscle-strengthening training protects against the occurrence and progression of cardiovascular disease and can improve cardiac function in heart failure patients. In the past decade significant advances have been made in identifying mechanisms of cardiomyocyte re-programming and renewal including an enhanced exercise-induced proliferational capacity of cardiomyocytes and its progenitor cells. Various intracellular mechanisms mediating these positive effects on cardiac function have been found in animal models of exercise and will be highlighted in this review. 1) activation of extracellular and intracellular signaling pathways including phosphatidylinositol 3 phosphate kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), EGFR/JNK/SP-1, nitric oxide (NO)-signaling, and extracellular vesicles; 2) gene expression modulation via microRNAs (miR), in particular via miR-17-3p and miR-222; and 3) modulation of cardiac cellular metabolism and mitochondrial adaption. Understanding the cellular mechanisms, which generate an exercise-induced cardioprotective cellular phenotype with physiological hypertrophy and enhanced proliferational capacity may give rise to novel therapeutic targets. These may open up innovative strategies to preserve cardiac function after myocardial injury as well as in aged cardiac tissue.
Highlights
Physical exercise has been shown to be protective against cardiovascular diseases (CVD), the leading cause of death worldwide [1]
Physiological hypertrophy is initiated via humoral factors and mechanical stress leading to changes in intracellular cardiac signaling to affect gene transcription, protein translation and modification, and metabolism [13]
Pathological hypertrophy, is associated with increased interstitial fibrosis, apoptosis, and loss of cardiomyocytes. It shows fetal gene expression, altered cell signaling, and a different metabolism with decreased fatty acid metabolism which results in cardiac dysfunction with increased risk of heart failure and sudden cardiac death compared to physiological cardiac hypertrophy in exercised hearts [19,20]
Summary
Physical exercise has been shown to be protective against cardiovascular diseases (CVD), the leading cause of death worldwide [1]. Different acute and chronic changes in autonomic regulation, cardiac metabolism, signaling pathways, and protein expression in exercising hearts leading to cardiac growth and cellular reprogramming have been discovered over recent years. Physiological hypertrophy is initiated via humoral factors and mechanical stress leading to changes in intracellular cardiac signaling to affect gene transcription, protein translation and modification, and metabolism [13]. These intracellular responses at a molecular level are different to those seen in pathological hypertrophy. In this context, exercise-modulated gene expression and cell signaling might protect the heart from further injuries and continuous maladaptive remodeling processes. We highlight these cellular mechanisms of cardiac remodeling in response to physical exercise with a focus on signaling pathways and microRNAs
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