Role of Antisense and Decoy Oligonucleotide of NF-κB in Vessel Stenosis and Neointima Formation in Balloon-Injured Rat Artery

Objective To examine antisense and decoy oligonucleotide of nuclear factor kappa B in vivo effects on intima proliferation and balloon-injured monocytes chemotactic protein-1 (MCP-1) and extracellular signal regulated kinase-2 (ERK2) expression in the carotid artery of rats. Methods Sprague-Dawley rats underwent balloon-dilation injury of the left carotid artery. Rats are divided into 7 groups (n=18) and each group includes 6 time points (6 h, 1, 3, 5, 7, 14 d) (n=3). Uninjured right carotid artery of the same rat was used as controls. Results In model group, sense group and scramble group, vessel intima area, media area and intima/media ratio increased after 5 d and reached the maximum after 7 d. The effect of antisense plus decoy group on intimal hyperplasia was more obvious than that of antisense group and decoy group alone. MCP-1 mRNA expression was increased expression continuously as 3, 5 and 7 d and decreased at 14 d. compared with model group, sense group and scramble group, antisense group, decoy group and antisense plus decoy group had lowered MCP-1 mRNA expression in each time point (P＜0.05). NF-κB p65 was dispersed positive stain 6 h after injury and increased after 1 d and peaked at 7 d, but the protein expression was weak at 14 d. ERK2 protein synthesis increased at 1 d and reached the peak at 7 d, while protein expression after 14 d was similar to that at 7 d. Treatment of antisense group, decoy group and antisense plus decoy group inhibited protein synthesis more significantly than those of model group, sense group and scramble group (P＜0.05). Conclusion NF-κB modulates genes expression and protein synthesis of MCP-1 and ERK2. Celluar proliferation in vessel wall was dynamically changed after balloon angioplasty injury. Antisense and decoy oligonucleotide of NF-κB by local lipofectamine transfer inhibit NF-κB activating gene modulation and neointimal hyperplasia.