Adventitial gene transfer of catalase attenuates angiotensin II-induced vascular remodeling

Vascular adventitia and adventitia-derived reactive oxygen species (ROS) contribute to vascular remodeling following vascular injury. A previous ex vivo study in adventitial fibroblasts showed that catalase, one of most important anti-oxide enzymes, was downregulated by angiotensin II (AngII). The aim of the present study was to investigate whether adventitial gene transfer of catalase affects AngII-induced vascular remodeling in vivo. Adenoviruses co-expressing catalase and enhanced green fluorescent protein (eGFP) or expressing eGFP only were applied to the adventitial surface of common carotid arteries of Sprague-Dawley rats. Alzet minipumps administering AngII (0.75 mg/kg/day) were then implanted subcutaneously for 14 days. Systolic blood pressure and biological parameters of vascular remodeling were measured in each group. Adventitial fibroblasts were cultured and p38 mitogen-activated protein kinase (MAPK) phosphorylation was measured using western blot analysis. The results showed that adventitial gene transfer of catalase had no effect on AngII-induced systolic blood pressure elevation. However, catalase adenovirus transfection significantly inhibited AngII-induced media hypertrophy compared with that of the control virus (P<0.05). In addition, catalase transfection significantly attenuated AngII-induced ROS generation, macrophage infiltration, collagen deposition and adventitial α-smooth muscle actin expression. Furthermore, catalase transfection significantly inhibited the AngII-induced increase in p38MAPK phosphorylation. In conclusion, the results of the present study demonstrated that adventitial gene transfer of catalase significantly attenuated AngII-induced vascular remodeling in rats via inhibition of adventitial p38MAPK phosphorylation.