Hashiya Naotaka, Aoki Motokuni, Tachibana Katsuro, Taniyama Yoshiaki, Yamasaki Keita, Hiraoka Kazuya, Makino Hirofumi, Yasufumi Kaneda, Ogihara Toshio, Morishita Ryuichi
Department of Geriatric Medicine, Osaka University, Graduate School of Medicine, Japan.
Biochem Biophys Res Commun. 2004 Apr 30;317(2):508-14. doi: 10.1016/j.bbrc.2004.03.070.
Since restenosis after angioplasty still remains a major clinical problems, inhibition of neointimal formation is an important subject. In this study, we focused on the transcription factor, E2F, that plays a pivotal role in the transactivation of cell-cycle regulatory genes, and also we developed a newly delivery system of decoy oligodeoxynucleotides (ODN). We transfected E2F decoy ODN mixed with an echo-contrast microbubble agent (Optison) into rat carotid artery balloon-injured model by using therapeutic ultrasound (US) to inhibit neointimal formation. Two weeks after transfection, the intimal to medial area ratio in E2F decoy+Optison+US group was significantly decreased (P < 0.01). Inhibition of cell growth was also confirmed by PCNA staining. No apparent toxicity such as inflammation could be detected in blood vessels transfected with E2F decoy ODN with Optison and ultrasound. Overall, the present studies demonstrated a novel non-viral ODN transfer method into blood vessels. A novel therapeutic strategy using E2F decoy ODN with Optison using ultrasound may be useful to inhibit restenosis in clinical practice without a viral vector.
由于血管成形术后再狭窄仍是一个主要的临床问题，抑制内膜增生是一个重要的研究课题。在本研究中，我们聚焦于转录因子E2F，其在细胞周期调控基因的反式激活中起关键作用，并且我们开发了一种新型的诱饵寡脱氧核苷酸（ODN）递送系统。我们通过治疗性超声（US）将与超声造影微泡剂（Optison）混合的E2F诱饵ODN转染到大鼠颈动脉球囊损伤模型中，以抑制内膜增生。转染两周后，E2F诱饵+Optison+US组的内膜与中膜面积比显著降低（P<0.01）。通过增殖细胞核抗原（PCNA）染色也证实了细胞生长受到抑制。在用Optison和超声转染E2F诱饵ODN的血管中未检测到明显的毒性，如炎症。总体而言，本研究证明了一种将新型非病毒ODN导入血管的方法。使用E2F诱饵ODN与Optison联合超声的新型治疗策略可能在临床实践中无需病毒载体即可有效抑制再狭窄。
