ROLE OF ANTISENSE AND DECOY OLIGONUCLEOTIDE OF NF-κB IN VESSEL STENOSIS AND NEOINTIMA FORMATION IN BALLOON-INJURED RAT ARTERY |
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| Authors: | ZHOU Jun LU Guo-ping QI Wen-hang |
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| Institution: | ZHOU Jun(Department of Cardiology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025,China)；LU Guo-ping(Department of Cardiology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025,China)；QI Wen-hang(Department of Cardiology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025,China)； |
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| Abstract: | Objective To examine antisense and decoy oligonucleotides 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 at 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. |
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