title: Novel E2F decoy oligodeoxynucleotides inhibit in vitro vascular smooth muscle cell proliferation and in vivo neointimal hyperplasia.
abstract: The transcription factor, E2F, plays a critical role in the trans-activation of several genes involved in cell cycle regulation. Previous studies showed that the transfection of cis element double-stranded decoy oligodeoxynucleotides (ODNs) corresponding to E2F binding sites inhibited the proliferation of vascular smooth muscle cells (VSMCs) and neointimal hyperplasia in injured vessels. We have developed a novel E2F decoy ODN with a circular dumbbell structure (CD-E2F) and compared its effects with those of the conventional phosphorothioated E2F decoy (PS-E2F) ODN. CD-E2F ODN was more stable than PS-E2F ODN, largely preserving its structural integrity after incubation in the presence of nucleases and sera. Moreover, CD-E2F ODN inhibited high glucose- and serum-induced transcriptional expression of cell cycle regulatory genes more strongly than PS-E2F ODN. Transfection of CD-E2F ODN resulted in more effective inhibition of VSMC proliferation in vitro and neointimal formation in vivo, compared with PS-E2F ODN. An approximately 40-50% lower dose of CD-E2F ODN than PS-E2F ODN was sufficient to attain similar effects. In conclusion, our results indicate that CD-E2F ODN may be a valuable tool in gene therapy protocols for inhibiting VSMC proliferation and studying transcriptional regulation.
authors.affiliation: Department of Microbiology, Kyungpook National University, Taegu, Korea.
authors.forename: J D
authors.initials: JD
authors.lastname: Ahn
authors.forename: R
authors.initials: R
authors.lastname: Morishita
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneda
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chang
authors.forename: K-U
authors.initials: KU
authors.lastname: Lee
authors.forename: J-Y
authors.initials: JY
authors.lastname: Park
authors.forename: H W
authors.initials: HW
authors.lastname: Lee
authors.forename: Y-H
authors.initials: YH
authors.lastname: Kim
authors.forename: I-K
authors.initials: IK
authors.lastname: Lee
mesh_terms: D000818:Animals; D001665:Binding Sites; D016893:Carotid Stenosis / Q000473:pathology / Q000628:therapy*; D018797:Cell Cycle Proteins; D002455:Cell Division; D002478:Cells, Cultured; D019925:Cyclin A / Q000235:genetics; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D017539:Tunica Intima / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins; D019925:Cyclin A; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors