Aerobic Training‑induced Upregulation of YAP1 and Prevention of Cardiac Pathological Hypertrophy in Male Rats

Abstract

Background: Pathological hypertrophy is one of the negative consequences of cardiac sympathetic hyperactivity. Recent studies have shown that YAP1 plays a critical role in cardiomyocytes
hypertrophy. Considering the preventive role of exercise training in cardiovascular diseases, the
present study was conducted to examine the effect of aerobic exercise training on YAP1 gene
expression and its upstream components.

Methods: Eighteen male Wistar rats were randomly divided
into aerobic training and control groups. Aerobic training was performed one hour/day, five days per
week, for eight weeks, on a treadmill at 65‑75% VO2 max. Pathological hypertrophy was induced
by injecting 3 mg/kg‑1 of isoproterenol for seven days. The left ventricle was separated, and YAP1,
3‑mercaptopyruvate sulfurtransferase (MST), large tumor suppressor (LATS), and mitogen‑activated
protein 4 kinase (MAP4K) gene expressions were assessed and YAP1 protein levels were also
assessed by western blotting. Cell apoptosis was detected by TUNEL assays. The between‑group
differences were evaluated using the T‑test and P value <0.05 was considered statistically significant.

Results: There were no significant between‑group differences in MST gene expression (P = 0.061);
meanwhile, in the training group, LATS and Map4K expressions were suppressed, followed by
a significant increase in YAP1 expression (P < 0.001). Compared to the control group, the left
ventricular weight increased significantly in the training group while the cardiomyocyte apoptosis
decreased.

Conclusions: The results showed that, by reducing LATS, aerobic training‑induced
YAP1 upregulation can help prevent the propagation of cardiomyocyte apoptosis due to pathological
conditions.