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1 University of Tsukuba, Institute of Health and Sport Sciences, Tsukuba, Japan; University of Tsukuba, Center for Tsukuba Advanced Research Alliance, Tsukuba, Japan
2 University of Tsukuba, Center for Tsukuba Advanced Research Alliance, Tsukuba, Japan; University of Tsukuba, Institute of Clinical Medicine, Tsukuba, Japan
3 Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Japan
* To whom correspondence should be addressed. E-mail: t-miyauc{at}md.tsukuba.ac.jp.
Exercise training improves aging-induced deterioration of angiogenesis in the heart. However, the mechanisms underlying exercise-induced improvement of capillary density in the aged heart are unclear. Vascular endothelial growth factor (VEGF) implicates in angiogenesis, which activated angiogenic signaling cascade through Akt and endothelial nitric oxide synthase (eNOS)-related pathway. We hypothesized that VEGF angiogenic signaling cascade in the heart contributes to a molecular mechanism of exercise training-induced improvement of capillary density in old age. The present study investigated whether VEGF and VEGF-related angiogenic molecular expression in the aged heart are affected by exercise training, using the hearts of sedentary young rats (4 months old), sedentary aged rats (23 months old), and exercise-trained aged rats (23 months old, swimming training for 8 weeks). Total capillary density in the heart was significantly lower in the sedentary aged rats compared with the sedentary young rats, whereas that in the exercise-trained rat was significantly higher than the sedentary aged rats. The mRNA and protein expressions of VEGF and of Flt-1 and Flk-1, which are main VEGF receptors, in the heart were significantly lower in the sedentary aged rats compared with the sedentary young rats, whereas those in the exercise-trained rats were significantly higher than the sedentary aged rats. The phosphorylation of Akt protein and eNOS protein in the heart corresponded to the changes in the VEGF protein levels. These findings suggest that exercise training improves aging-induced downregulation of cardiac VEGF angiogenic signaling cascade, thereby contributing to the exercise training-induced improvement of angiogenesis in old age.
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