Inhibition of phenotype modulation, growth, and migration of vascular smooth muscle cells by a guanosine-rich 30-mer phosphorothioate oligodeoxynucleotide.
The testing of a 30-mer dG-rich phosphorothioate oligodeoxynucleotide (LG4PS) for effects on the behaviour of vascular smooth muscle cells (VSMC) in vitro and in vivo is described. LG4PS at 0.3 microM inhibited significantly the phenotype modulation of freshly isolated rabbit VSMC, and cell outgrowth from pig aortic explants was inhibited approximately 80% by 5 microM LG4PS. The growth of proliferating rabbit and pig VSMC was inhibited approximately 70% by 0.3 microM and 5 microM 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 VSMC in vitro were low. Despite these promising results, adventitial application of 2-200 nmol LG4PS in pluronic gel failed to reduce vascular hyperplasia in balloon-injured rabbit carotid arteries, and the highest dose caused extensive mortality.
Graham
L D
LD
Cooperative Research Centre for Cardiac Technology, University of Queensland, St Lucia, Australia.
Hayward
I P
IP
Fitzgerald
M
M
Whitelock
J M
JM
Bingley
J A
JA
Campbell
J H
JH
Underwood
P A
PA
D000818:Animals; D001011:Aorta; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006151:Guanosine; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008323:Mammary Arteries; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010641:Phenotype; D011817:Rabbits; D013552:Swine; D013873:Thionucleotides
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D006151:Guanosine; D006493:Heparin