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Research Article Free access | 10.1172/JCI118810
Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA.
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Published July 15, 1996 - More info
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.