Effects of moderate - intensity exercise training on cardiac angiogenic capacity and fibrosis in middle-aged and aged rats

Abstract

This study aimed to investigate the protective effects of exercise training against age-induced the reduction of cardiac angiogenic capacity associated with p-Akt1, eNOS, Mdm2, p53, VEGF, and CD31 in rat hearts. Additionally, age-induced cardiac fibrosis association with TGF-β1 was also observed. Male Wistar rats were divided into five groups: Sedentary - young group (SE-Young, aged 4 months), Sedentary - middle-aged group (SE-Mid-Age, 14 months), Sedentary – aged group (SE-Age, aged 22 months), Exercise-trained middle-aged group (ET-Mid-Age, aged 14 months), and Exercise-trained -aged group (ET-Age, aged 22 months). In the SE- groups, rats were immersed individually for 30 minutes/day, 5 days/week for 8 weeks in cylindrical tanks filled with water; depth of 5 cm, the temperature at 33-36 oC. In ET groups, rats swam individually for 60 minutes/day, 5 days/week for 8 weeks in cylindrical tanks filled with water; depth of 50-55 cm, the temperature at 33-36 oC. After 8 weeks of exercise training, the rats were rest for 24 hours before the experiment. The rats were measured blood pressure and assessed the expression of p53, Mdm2, CD31, collagen accumulation by using immunohistochemistry and Masson's Trichrome Staining, respectively. Heart homogenates were used for the assay of malondialdehyde levels (MDA) by using the thiobarbituric acid reactive substances assay (TBARS) and the levels of p-Akt1, eNOS, VEGF and TGF-β1 using enzyme-linked immunosorbent assay (ELISA). Our results showed that the SE-Age group had significantly high blood pressure when compared to the SE-Young and SE-Mid-Age. The ET-Age group showed significantly decreased blood pressure when compared to SE-Age. The ET-Mid-Age group showed a lower blood pressure than in the SE-Mid-Age group, but not yet significant. The levels of p-Akt1, eNOS, VEGF, and CD31 were significantly increased in all ET groups when compared with SE–Mid-Age and SE-Age. Mdm2 levels were significantly increased in SE-Young when compared to SE-Mid-Age and SE-Age. Only Mdm2 levels in the ET-Age had a significant increase when compared to SE-Age, while no significant difference of p53 in all groups. The collagen accumulation and TGF-β1 levels were significantly increased in SE-Age when compared to SE-Young and exercise training could reduce these. Furthermore, tissue MDA in ET-Mid-Age and ET-Age rats were significantly reduced when compared to SE-Mid-Age and SE-Age control. Therefore, these results implied that the exercise training program used in this study prevented age-induced the reduction of angiogenic capacity and fibrosis, and these results were associated with its effects on oxidative stress, p-Akt, eNOS, Mdm2, p53, VEGF, CD31, and TGF-β1.