Neointimal formation is exacerbated following vascular injury in p22^phox overexpressing transgenic mice

Abstract

These studies tested the hypothesis that transgenic mice overexpressing the p22phox subunit of the NAD(P)H oxidase selectively in smooth muscle (Tgp22smc) would exhibit exacerbated neointimal formation following mechanically induced transluminal vascular injury compared to wild‐type control mice. Tgp22smc mice have a two‐fold increase in p22phox expression and H2O2 production; thus providing a model to examine the effects of elevated vascular ROS production on VSMC function in vivo. To induce vascular injury, a 0.36 mm steel catheter was guided 4–5 mm into the left common carotid via the external carotid. Following one minute the catheter was removed and reperfusion verified. The degree of neointimal formation was assessed by morphological analysis of wall thickness (WT) and cross‐sectional wall area (CSWA) in male Tgp22smc mice and littermate controls 14 days following injury. WT following injury indicated significantly greater neoinitimal formation in Tgp22smc mice (54.3 ± 7.3 vs. 43.7 ± 4.1 μm), while non‐injured contralateral carotids were similar between groups (28.5 ± 3.3 vs. 33.8 ± 2.8 μm). Moreover, the increase in carotid artery CSWA following injury was approximately four‐fold greater in Tgp22smc mice compared to control animals. Findings from these in vivo studies strongly support in vitro data which has implicated ROS as a crucial mediator of both VSMC proliferation and migration. AHA 03300119N