MicroRNAs Regulate Cardiomyocyte Calcium Signaling in Heart Diseases: The Potential Role of Exercise Training

ABSTRACT Heart diseases continue to be a leading global health challenge, significantly contributing to morbidity, mortality, and healthcare burdens. A critical aspect of heart disease pathophysiology is the disruption of calcium ion (Ca 2+ ) homeostasis, which is central to excitation‐contraction coupling in cardiomyocytes. Dysregulation of intracellular Ca 2+ dynamics is associated with conditions such as hypertension, diabetes, and heart failure, and impairs cardiomyocyte function, leading to progressive cardiac dysfunction. Recent research highlights the potential of physical training, particularly aerobic and resistance modalities, in restoring Ca 2+ homeostasis and improving cardiac function. Exercise‐induced modulation of microRNAs (miRNAs) plays a crucial role in this process. miRNAs regulate post‐transcriptional gene expression and influence key proteins involved in Ca 2+ signaling pathways, such as the ryanodine receptor type 2, sarcoplasmic/endoplasmic reticulum Ca 2+ ‐ATPase 2a, and sodium‐calcium exchanger. Dysregulation of these miRNAs exacerbates cardiac dysfunction. This review explores the interplay between miRNAs, Ca 2+ homeostasis, and physical exercise training in the context of heart diseases, emphasizing the potential of exercise‐induced miRNA modulation as a therapeutic strategy to improve cardiac function and positively impact prevention, treatment, and management of disease progression.