Inhibitory Effects of Novel AP-1 Decoy Oligodeoxynucleotides on Vascular Smooth Muscle Cell Proliferation In Vitro and Neointimal Formation In Vivo

• DOI: 10.1161/01.res.0000023200.19316.d5
• Publication Date: 2002-07-28T23:16:07Z
• Authors: Jong Deok Ahn; Ryuichi Morishita; Yasufumi Kaneda; Sang-Jun Lee; Ki-Young Kwon; Se-Young Choi; Ki-Up Lee; Joong-Yeol Park; Ik-Jae Moon; Jong-Gu Park; Masao Yoshizumi; Yasuyoshi Ouchi; In-Kyu Lee
• Keywords: Decoy; Neointimal hyperplasia; Neointima

Excessive proliferation of vascular smooth muscle cells (VSMCs) and neointimal formation are critical steps in the pathogenesis atherosclerosis restenosis after percutaneous transluminal angioplasty. In this study, we investigated hypothesis that activator protein-1 (AP-1) plays an important role injury. A circular dumbbell AP-1 decoy oligodeoxynucleotide (CDODN) was developed as a novel therapeutic strategy for This CDODN more stable than conventional phosphorothioate linear ODN (PSODN) maintained structural integrity on exposure to exonuclease III or serum. Transfection with ODNs strongly inhibited VSMC migration, well glucose- serum-induced expression PCNA cyclin genes. Administration vivo using hemagglutinating virus Japan (HVJ)-liposome method virtually abolished balloon injury rat carotid artery. Compared PSODN, effective inhibiting VSMCs vitro vivo. Our results collectively indicate activation is crucial mediation response Moreover, use specific activity combination highly HVJ-liposome provides potential prevention angioplasty humans.