INHIBITION OF PHENOTYPE MODULATION,GROWTH, AND MIGRATION OF VASCULAR SMOOTH MUSCLE CELLS BY A GUANOSINE-RICH 30-MER PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE |
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| Authors: | L D GRAHAM I P HAYWARD M FITZGERALD J M WHITELOCK J A BINGLEY J H CAMPBELL P A UNDERWOOD |
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| Institution: | 1. Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße, 38-40-1090 Vienna, Austria;2. Core Facility Multimodal Imaging, Faculty of Chemistry, University of Vienna, Währingerstraße, 38-40-1090 Vienna, Austria |
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| Abstract: | The testing of a 30-mer dG-rich phosphorothioate oligodeoxynucleotide (LG4PS) for effects on the behaviour of vascular smooth muscle cells (VSMC)in vitroandin vivois described. LG4PS at 0.3μm inhibited significantly the phenotype modulation of freshly isolated rabbit VSMC, and cell outgrowth from pig aortic explants was inhibited ～80% by 5μm LG4PS. The growth of proliferating rabbit and pig VSMC was inhibited ～70% by 0.3μm and 5μm LG4PS, respectively. Though less marked, the antiproliferative effects of LG4PS on human VSMC were comparable to those obtained with heparin. The cytotoxic effects of LG4PS on VSMCin vitrowere low. Despite these promising results, adventitial application of 2–200nmol LG4PS in pluronic gel failed to reduce vascular hyperplasia in balloon-injured rabbit carotid arteries, and the highest dose caused extensive mortality. |
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| Keywords: | vascular smooth muscle phosphorothioate phenotype modulation hyperplasia antiproliferative balloon catheter arterial injury heparin |
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