Moderate Aerobic Training Inhibits Middle-Aged Induced Cardiac Calcineurin-NFAT Signaling by Improving TGF-beta, NPR-A, SERCA2, and TRPC6 in Wistar Rats

Objective: The purpose of this study was to investigate the effect of moderate-intensity training on the calcineurin/nuclear factor of activated t-cells (NFAT) pathway and factors affecting it in the middle-age Wistar rats. Materials and Methods: In this experimental study, 40 young (n=10, 4-month-old) and middle-aged (n=30, 13-15 months old) Wistar rats were included in this experimental study. All young and 10 middle-aged rats did not training and served as a control comparision; while the remaining 20 middle-aged rats were trained at moderate intensity for 4-weeks (n=10) or 8-weeks (n=10) on a treadmill (speed: 16 m/minutes, slope: 0%, distance: 830 m, duration: 54 minutes). Results: Calcineurin tissue expression was increased in the middle-aged control rats compared to the young control rats (P=0.001). Expression of sarco/endoplasmic reticulum Ca2+-ATPase (SERC2A), natriuretic peptide receptor-A (NPR-A), phospholamban (PLB), plasma membrane Ca(2+)ATPase (PMCA4b), and p-AKT was significantly decreased in the heart tissue of middle-aged control compared to the young control rats (P=0.001). Furthermore, transforming growth factor beta (TGF-beta), including transient receptor potential canonical 6 (TRPC6), were up-regulated in the heart tissue of middle-aged control compared to the young control rats (P=0.001). However, aerobic training inhibited this pathway and reversed all changes in the trained middle-aged rats. Conclusion: Aerobic training effectively inhibited the calcineurin/NFATc pathway and modulated intracellular Ca2+ levels at least partially by restoring NPR-A, SERCA2, p-PLB, and p-AKT, and decreasing TRPC6 and TGF-beta levels.