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. 1996 Jul 15;98(2):443–450. doi: 10.1172/JCI118810

Sequence-independent inhibition of in vitro vascular smooth muscle cell proliferation, migration, and in vivo neointimal formation by phosphorothioate oligodeoxynucleotides.

W Wang 1, H J Chen 1, A Schwartz 1, P J Cannon 1, C A Stein 1, L E Rabbani 1
PMCID: PMC507448  PMID: 8755655

Abstract

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.

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Selected References

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