Attenuating cardiac fibrosis and apoptosis by exercise is associated with modulation of the circSlc8a1/miR-133a axis in D-galactose-treated rats

Abstract Purpose Circular RNAs and microRNAs have been identified as key regulators of aging mechanisms and cardiovascular disorders. This study investigated the effects of moderate-intensity endurance training (MIET) and high-intensity interval training (HIIT) on cardiac fibrosis- and apoptosis-related markers and their relationship with the circSlc8a1/miR-133a axis in a D-galactose-induced aging model of male rats. Method Forty-two male Wistar rats were randomly assigned to six groups: control (CTL), MIET, HIIT, D-galactose (D-gal), D-gal+MIET, and D-gal+HIIT. Exercise training was conducted for 8 weeks, five days per week, concurrently with daily D-galactose injections. Expression levels of circSlc8a1 and miR-133a were quantified by real-time PCR, and protein levels of fibrosis (TGF-β, CTGF) and apoptosis (Bim, BMF) markers were measured via western blot analysis. Results Results: Both MIET and HIIT attenuated the D-gal-associated changes in circSlc8a1 and miR-133a expression, characterized by increased circSlc8a1 and decreased miR-133a expression. Moreover, both exercise interventions were accompanied by lower levels of the fibrosis- and apoptosis-related markers TGF-β, CTGF, Bim, and BMF compared with the D-gal-treated group. Conclusion The present findings suggest that exercise training may attenuate D-galactose-induced cardiac changes and is associated with modulation of the circSlc8a1/miR-133a axis, accompanied by lower levels of markers related to myocardial fibrosis and apoptosis. These results support the potential role of exercise as a non-pharmacological strategy for mitigating aging-associated cardiac changes; however, further studies are needed to clarify the underlying mechanisms and functional implications.