Radiotherapy inhibits neointimal hyperplasia after artificial vascular replacement through Skp2/P27kip1

We aimed to establish an animal model of abdominal aortic vascular replacement in mongrel dogs to investigate the effect of extracorporeal radiotherapy on the intima. Twenty healthy mongrel dogs were randomly divided into four groups: 5-week control group, 5-week radiotherapy group, 10-week control group and 10-week radiotherapy group. We first performed an artificial vascular replacement of the abdominal aortic segment. The radiotherapy group received external radiotherapy with a dose of 7 Gy for 4 days. The thickness of neointimal hyperplasia, immunoreactivity and expression of proliferation-related factors were detected by hematoxylin and eosin (HE) staining, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR )and western blotting at 5 and 10 weeks after the reconstruction. The results showed that the intimal thickness of the artificial blood vessel in the 5- and 10-week radiotherapy groups was thinner than that in the control groups by HE staining. The immunoreactivity and expression levels of Skp2, c-Myc and CyclinE1 were significantly decreased in the radiotherapy groups than those in control groups by immunohistochemistry, qRT-PCR and western blotting. On the contrary, immunoreactivity and expression levels of P27(kip1) were increased. In conclusion, we discovered that postoperative external radiotherapy significantly decreases the intimal hyperplasia of artificial blood vessels by regulating c-Myc-Skp2-P27-CyclinE1 network.