백서의 혈관 평활근 세포 증식에 대한 E2F Decoy Oligodeoxynucleotides의 효과
- Author(s)
- 김미정; 김혜순; 한성욱; 이인규; 박남희; 최세영; 김기식
- Keimyung Author(s)
- Kim, Hye Soon; Han, Seong Wook; Lee, In Kyu; Kim, Kee Sik; Park, Nam Hee; Choi, Sae Young
- Department
- Dept. of Internal Medicine (내과학)
Dept. of Thoracic & Cardiovascular Surgery (흉부외과학)
- Journal Title
- 한국지질동맥경화학회
- Issued Date
- 2003
- Volume
- 13
- Issue
- 2
- Keyword
- E2F decoy; Neointimal formation; VSMC proliferation; Balloon injury
- Abstract
- Background : Excessive proliferation of vascular smooth muscle cells (VSMCs) and neointimal formation are
critical steps in the pathogenesis of restenosis after percutaneous transluminal angioplasty (PTCA). The transcription
factor, E2F, plays a critical role in transactivation of several genes involved in cell cycle regulation. In the present
study, we investigated the hypothesis that transfection of cis-element double-stranded decoy oligodeoxynucleotides
(ODNs) corresponding to E2F binding sites inhibits the proliferation of VSMCs and neointimal hyperplasia.
Methods : We evaluated gene expression and proliferation in rat VSMCs under high D-glucose and serum, and
after transfection of E2F decoy ODNs in vitro. And we also evaluated neointimal formation in vivo model of rat
carotid injury.
Results : Transfection with E2F decoy ODNs inhibited VSMCs proliferation (p<0.05). Transfection of E2F decoy
ODNs attenuated DNA binding activity (p<0.001) and promoter activity of E2F induced by high glucose and serum
(P<0.01) E2F decoy ODNs also attenuated glucose- and serum-induced expression of cyclin A and PCNA genes
(p<0.01). Administration of E2F decoy ODNs in vivo using the hemagglutinating virus of Japan (HVJ)-liposome
method virtually abolished neointimal formation after ballon injury to the rat carotid artery (P<0.01).
Conclusion : Conclusions: This study shows that transfection of E2F decoy ODNs may decrease cell cycle
regulatory gene expression, cell proliferation and vascular lesion formation in vitro and in vivo. Our results provide
a novel potential therapeutic strategy for the prevention of restenosis after angioplasty.
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