백서의 혈관 평활근 세포 증식에 대한 E2F Decoy Oligodeoxynucleotides의 효과

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.