Abstract
OBJECTIVES: To investigate the mechanism by which aerobic exercise improves transverse aortic constriction (TAC)-induced heart failure in mice. METHODS: Thirty male C57BL/6J mice were randomized into sham-operated group, TAC model group, and TAC with aerobic exercise (TACE) group. The mice in TACE group underwent a 4-week progressive treadmill training starting on day 3 following TAC modeling. Echocardiography and Masson's trichrome staining were used to assess cardiac function and myocardial fibrosis of the mice, respectively, and serum levels of BNP, TNF-α, IL-6, IL-1β, MDA, SOD, and GSH-Px were measured using ELISA. The mRNA and protein expressions of Hippo-YAP pathway components in the myocardial tissue were detected using RT‑PCR and Western blotting, respectively. Bioinformatics analysis was performed to explore the correlations among the measured indicators. RESULTS: Compared with those in TAC group, the mice in TACE group showed significantly reduced heart weight and heart weight/body weight ratio, increased left ventricular ejection fraction, left ventricular fractional shortening, and E/A ratio, reduced myocardial fibrosis, decreased BNP expression in both the serum and myocardial tissue, lowered serum levels of TNF‑α, IL‑6, IL‑1β, and MDA, and increased SOD and GSH-Px activities. The mRNA expressions of Mst1, Lats1, Lats2, and YAP1 were significantly downregulated in TACE group as compared with those in TAC group. Western blotting revealed decreased total protein expressions of Mst1/2, Lats1/2, and YAP and increased expression levels of phosphorylated Lats1/2 and phosphorylated YAP in TACE group. Correlation analysis suggested significant associations of oxidative stress markers and inflammatory factors with the expressions of the Hippo-YAP pathway components. CONCLUSIONS: Aerobic exercise improves cardiac function and attenuates cardiac remodeling in mice with TAC-induced heart failure possibly by suppressing oxidative stress and inflammation and modulating the Hippo-YAP pathway.