Sequence-independent inhibition of in vitro vascular smooth muscle cell proliferation, migration, and in vivo neointimal formation by phosphorothioate oligodeoxynucleotides.
Sequence-independent inhibition of in vitro vascular smooth muscle cell proliferation, migration, and in vivo neointimal formation by phosphorothioate oligodeoxynucleotides.
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硫代磷酸寡脱氧核苷酸对体外血管平滑肌细胞增殖、迁移和体内新内膜形成的序列独立抑制。
DOI：
10.1172/jci118810
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Rabbani,LE
中科院分区：
文献类型：
--
作者：
Wang,W;Chen,HJ;Schwartz,A;Cannon,PJ;Stein,CA;Rabbani,LE
硫代磷酸寡脱氧核苷酸 (PS 寡核苷酸) 是针对不同基因时血管平滑肌细胞 (SMC) 增殖的反义（序列特异性）抑制剂。最近，PS 寡核苷酸的适配体 G 四联体抑制作用已得到证实。为了确定 PS 寡核苷酸是否对人主动脉 SMC 表现出非 G 四联体、非序列特异性作用，我们检查了 S-dC28（一种 28 聚体硫代磷酸胞苷均聚物）对几种 SMC 有丝分裂原诱导的 SMC 增殖的影响。 S-dC28 显着抑制 10% FBS 以及有丝分裂剂 PDGF、bFGF 和 EGF 诱导的 SMC 增殖，且无细胞毒性。此外，S-dC28 在改良的微型博伊登室中消除了 PDGF 诱导的体外迁移。此外，S-dC28 在大鼠颈动脉球囊损伤模型中表现出体内抗增殖作用。 S-dC28 将新内膜横截面积抑制了 73%，将内膜/中膜面积比抑制了 59%。因此，PS 寡核苷酸对体外 SMC 增殖和迁移以及体内新内膜形成发挥有效的非 G 四重奏、非序列特异性作用。
Phosphorothioate oligodeoxynucleotides (PS oligos) are antisense (sequence-specific) inhibitors of vascular smooth muscle cell (SMC) proliferation when targeted against different genes. Recently an aptameric G-quartet inhibitory effect of PS oligos has been demonstrated. To determine whether PS oligos manifest non-G-quartet, non-sequence-specific effects on human aortic SMC, we examined the effects of S-dC28, a 28-mer phosphorothioate cytidine homopolymer, on SMC proliferation induced by several SMC mitogens. S-dC28 significantly inhibited SMC proliferation induced by 10% FBS as well as the mitogens PDGF, bFGF, and EGF without cytotoxicity. Moreover, S-dC28 abrogated PDGF-induced in vitro migration in a modified micro-Boyden chamber. Furthermore, S-dC28 manifested in vivo antiproliferative effects in the rat carotid balloon injury model. S-dC28 suppressed neointimal cross-sectional area by 73% and the intima/media area ratio by 59%. Therefore, PS oligos exert potent non-G-quartet, non-sequence-specific effects on in vitro SMC proliferation and migration as well as in vivo neointimal formation.