Inhibition of Neointimal Hyperplasia Development by MCI-186 is Correlated With Downregulation of Nuclear Factor-κB Pathway

Abstract

Background Atherosclerosis is a progressing inflammatory response mediated by various signaling molecules among which nuclear factor κB (NF-κB) is thought to have a pivotal role. This study demonstrated the efficacy of antioxidant MCI-186 in preventing the progression of atherosclerosis by inhibiting signaling molecules such as NF-κB. Methods and Results Balloon injury of intima was performed in the right common carotid artery of Japanese male white rabbits, which were then fed a 1% high cholesterol diet for 4 weeks, after assigning them to either the control (n=7) or MCI-186 (0.5 mg ·kg^-1 · day^-1, n=7) group. Histological analysis revealed a reduction in neointimal thickness and lipid deposition in the subendothelial area of the MCI-186 group. Immunohistochemical analysis revealed attenuation of E-selectin expression, macrophage migration and proliferation of smooth muscle cells in the MCI-186 treated group. In in vitro studies, rabbit aorta smooth muscle cells were incubated with rIL-1βin either the presence or absence of MCI-186. MCI-186 significantly inhibited rIL-1β-induced proliferation of smooth muscle cells from rabbit aorta, as well as the activation of NF-κB. Moreover, western blot analysis showed the inhibitory action of MCI-186 on the nuclear translocation of NF-κB in human umbilical vein endothelial cells under rIL-1βstimulation. Conclusions MCI-186 could provide a novel therapeutic strategy for atherosclerosis by inhibiting the NF-κB pathway. (Circ J 2008; 72: 800 - 806)