Effect of cystatin C on adventitia in restenosis after rabbit aorta angioplasty

Objective To investigate the effect of cystatin C (Cys C) on adventitia in rabbit abdominal aorta restenosis after angioplasty and its mechanism. Methods 48 New Zealand white rabbits were randomly divided into injury group (receiving balloon dilation of abdominal aorta), the treatment group (taking Cys C monoclonal antibody therapy) and the control group (receiving femoral artery puncture and catheter sheath without balloon dilation and intervention of Cys C monoclonal antibody injection), and each group had 16 rabbits.Peripheral vein blood was drawn to measure the serum level of cystatin C before and 8 h, 1 day, 1 week, 3 weeks, 6 weeks after the operation in all rabbits.After 6 weeks of operation, the abdominal aorta were taken and stained with HE.Vascular morphometry analysis and adventitial cell count were conducted.Smooth muscle actin (SM-actin) and proliferating cell nuclear antigen (PCNA) expressions in the adventitia were observed by immunohistochemical staining.The number of PCNA positive cell in the adventitia was counted and the PCNA proliferation index was calculated.The vascular remodeling index, vascular external elastic lamina area (EELA), internal elastic lamina area (IEIA) were used to evaluate the vascular remodeling and the residual stenosis and vascular cavity area was used to measure the vascular stenosis. Results Plasma Cys C level began to rise at 8h after operation and reached the peak at 1 week after operation, and continuously increased for 5 weeks in injury group, and reached to respectively at 3 weeks and 6 weeks after operation.The Cys C levels were significantly higher in injury group than in the treatment and control groups at different time points (all P<0.05). There were no significant differences in Cys C levels at different time points between the treatment group and the control group.The injury group showed that the number of PCNA positive cells was higher in injury group than in treatment and control groups, both P<0.05). Compared with the control group, the vascular luminal area, EELA and IELA were significantly increased (all P<0.05). After treated with the monoclonal antibody Cys C intervention, the treatment group showed that lumen area, vascular EELA, IELA was significantly decreased (P<0.05), and the vascular remodeling index and residual stenosis rate were decreased as compared with the injury group (0.871 vs.0.784, 33.1% vs.19.7%, both P<0.05). Correlation analysis showed that Cystatin C level was positively correlated with the vascular lumen area, neointimal area, internal elastic lamina area, external elastic lamina area and the number of PCNA positive cells (r=0.812, 0.797, 0.876, 0.932 and 0.822 respectively, all P<0.01). Conclusions Plasma Cys C level is increased in rabbit after abdominal aorta balloon injury and has a positive correlation with the severity of arterial stenosis.High Cys C level can induce adventitial fibroblast activation, proliferation, phenotype transformation and migration, and accelerate the processes of atherosclerosis and stenosis.Cys C level is the independent risk factor for abdominal aortic stenosis. Key words: Cyalones; Aorta, abdominal; Angioplasty