The aim of this study was to investigate whether inhibiting the activation of angiotensin II type 1 receptor (AT1) could prevent severe muscle atrophy after denervation. The study found that AT1a receptor deficiency resulted in a significant attenuation of muscle weight and cross-sectional areas of type IIb muscle fibers in denervated muscles compared to wild-type mice. It was also observed that gene expressions related to protein degradation, as well as the activation of nuclear factor kappa B and Forkhead box subgroup O1, were significantly lower in AT1a(-/-) mice. In addition, the AT1a(-/-) mice showed suppressed apoptosis, lower infiltration of M1 macrophages, and higher infiltration of M2 macrophages compared to the wild-type mice. These findings suggest that AT1 receptor deficiency can retard muscle atrophy after denervation.
The study aim was to determine if suppressed activation of angiotensin II type 1 receptor (AT1) prevents severe muscle atrophy after denervation. The sciatic nerves in right and left inferior limbs were cut in AT1a knockout homo (AT1a(-/-)) male mice and wild-type (AT1a(+/+)) male mice. Muscle weight and cross-sectional areas of type IIb muscle fibers in gastrocnemius muscle decreased at 7 and 21 days postdenervation in both AT1a(-/-) mice and AT1a(+/+) mice, and the reduction was significantly attenuated in the denervated muscles of AT1a(-/-) mice compared to the AT1a(+/+) mice. Gene expressions in the protein degradation system [two E3 ubiquitin ligases (muscle RING-finger protein-1 and Atrogin-1)] upregulated at 7 days postdenervation in all denervated mice were significantly lower in AT1a(-/-) mice than in AT1a(+/+) mice. Activations of nuclear factor kappa B and Forkhead box subgroup O1, and protein expression of monocyte chemoattractant protein-1 were significantly suppressed in the AT1a(-/-) mice compared with those in the AT1a(+/+) mice. In addition, suppressed apoptosis, lower infiltration of M1 macrophages, and higher infiltration of M2 macrophages were significantly observed at 21 days postdenervation in the AT1a(-/-) mice compared with those in the AT1a(+/+) mice. In conclusion, the AT1 receptor deficiency retarded muscle atrophy after denervation.
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