Novel E2F decoy oligodeoxynucleotides inhibit in vitro vascular smooth muscle cell proliferation and in vivo neointimal hyperplasia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2002-11-29

AUTHORS

J D Ahn, R Morishita, Y Kaneda, H S Kim, Y-C Chang, K-U Lee, J-Y Park, H W Lee, Y-H Kim, I-K Lee

ABSTRACT

The transcription factor, E2F, plays a critical role in the trans-activation of several genes involved in cell cycle regulation. Previous studies showed that the transfection of cis element double-stranded decoy oligodeoxynucleotides (ODNs) corresponding to E2F binding sites inhibited the proliferation of vascular smooth muscle cells (VSMCs) and neointimal hyperplasia in injured vessels. We have developed a novel E2F decoy ODN with a circular dumbbell structure (CD-E2F) and compared its effects with those of the conventional phosphorothioated E2F decoy (PS-E2F) ODN. CD-E2F ODN was more stable than PS-E2F ODN, largely preserving its structural integrity after incubation in the presence of nucleases and sera. Moreover, CD-E2F ODN inhibited high glucose- and serum-induced transcriptional expression of cell cycle regulatory genes more strongly than PS-E2F ODN. Transfection of CD-E2F ODN resulted in more effective inhibition of VSMC proliferation in vitro and neointimal formation in vivo, compared with PS-E2F ODN. An approximately 40–50% lower dose of CD-E2F ODN than PS-E2F ODN was sufficient to attain similar effects. In conclusion, our results indicate that CD-E2F ODN may be a valuable tool in gene therapy protocols for inhibiting VSMC proliferation and studying transcriptional regulation. More... »

PAGES

1682-1692

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.gt.3301849

DOI

http://dx.doi.org/10.1038/sj.gt.3301849

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1048568841

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12457282


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