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Cell Biology International (1997) 21, 585–594 (Printed in Great Britain)

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INHIBITION OF PHENOTYPE MODULATION, GROWTH, AND MIGRATION OF VASCULAR SMOOTH MUSCLE CELLS BY A GUANOSINE-RICH 30-MER PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE

L.D. GRAHAM^a,f1, I.P. HAYWARD^b, M. FITZGERALD^b, J.M. WHITELOCK^a, J.A. BINGLEY^b, J.H. CAMPBELL^b and P.A. UNDERWOOD^a

^aCooperative Research Centre for Cardiac Technology, CSIRO Molecular Science, P.O. Box 184, North Ryde, NSW, 2113
^bDepartment of Anatomy, University of Queensland, St Lucia, Queensland, 4072, Australia

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 0.3μminhibited significantly the phenotype modulation of freshly isolated rabbit VSMC, and cell outgrowth from pig aortic explants was inhibited ∼80% by 5μmLG4PS. The growth of proliferating rabbit and pig VSMC was inhibited ∼70% by 0.3μmand 5μmLG4PS, 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.

Key words: vascular smooth muscle, phosphorothioate, phenotype modulation, hyperplasia, antiproliferative, balloon catheter, arterial injury, heparin.

^f1*To whom correspondence should be addressed.