GW24-e2479 AVE0991 inhibits vascular remodelling in rat jugular vein grafts via reduced ERK1/2 and p38 MAPK activity

Objectives To evaluate the effects of AVE0991 on vascular remodelling in vein grafts. Methods A model of autologous jugular vein grafts in rats was established. With this model system, rats (n = 16 per group) underwent autologous jugular vein graft transplantation (AVE0991 and control groups), or a sham operation (sham group) in which grafting was not performed. Three days after operation, all rats were treated with AVE0991(1mg/kg/d) (AVE0991 group) or PEG-400(0.5ml/d) (control and sham groups) by adminstration. Results After 4 weeks, weight, blood pressure and heart rate were not significantly different between groups. Typical venous-graft hyperplasia, vascular remodelling, ERK1/2 activity, p38 MAPK activity and proliferating cell nuclear antigen (PCNA) and a-smooth muscle actin (a-SMA) expression present in the control group were attenuated by AVE0991 treatmen. Tissue angiotensin II expression was increased in the AVE0991 and control groups but was not different between the groups. Conclusions The results of the present study indicate that AVE0991 interferes with the vascular remodelling of autologous jugular vein grafts and significantly inhibits vein-graft intimal hyperplasia via inhibition of vascular tissue ERK1/2 and p38 MAPK activation. Thus, AVE0991 improves the outcome of vein grafting via attenuation of vascular remodelling.