Effect of BO-653 and probucol on c-MYC and PDGF-A messenger RNA of the iliac artery after balloon denudation in cholesterol-fed rabbits.
Antioxidants have been proposed as a promising treatment for restenosis after percutaneous transluminal coronary angioplasty (PTCA), but their mechanism of action remains unclear. Here, we investigated the effect of antioxidants on gene expression in the artery after balloon denudation. We developed a sensitive ribonuclease (RNase) protection assay for the messenger RNA (mRNA) levels of immediate early (IE) genes (c-jun, c-fos and c-myc), as well as platelet-derived growth factor-A (PDGF-A), platelet-derived growth factor-beta receptor, transforming growth factor-beta 1, and vascular endothelial growth factor. New Zealand White rabbits were fed a 0.17% cholesterol diet containing vehicle, BO-653 or probucol, and balloon denudation for iliac arteries was performed. The iliac arteries were then removed at 4 h after the denudation, for IE genes, and 10 days after for growth factors and receptors. Both BO-653 and probucol significantly reduced neointimal thickening, compared with the control. In terms of gene expression, BO-653, but not probucol, significantly inhibited c-myc induction. On the other hand, probucol, but not BO-653, significantly inhibited PDGF-A expression. Neither treatment had any effect on the expression of other genes. These results suggest that antioxidants affect the gene expression of the neointimal response and that both BO-653 and probucol inhibit gene expression in specific manners.
Inoue
Kenji
K
Department Molecular Biology and Medicine, The University of Tokyo, Tokyo, Japan.
Cynshi
Osamu
O
Kawabe
Yoshiki
Y
Nakamura
Minako
M
Miyauchi
Katsumi
K
Kimura
Tohoru
T
Daida
Hiroyuki
H
Hamakubo
Takao
T
Yamaguchi
Hiroshi
H
Kodama
Tatsuhiko
T
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000235:genetics / Q000628:therapy; D001483:Base Sequence; D001572:Benzofurans / Q000494:pharmacology*; D002404:Catheterization; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D015870:Gene Expression; D016259:Genes, myc / Q000187:drug effects* / Q000235:genetics; D007083:Iliac Artery / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000187:drug effects* / Q000235:genetics; D011336:Probability; D011341:Probucol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction
C106512:2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran; D000975:Antioxidants; D001572:Benzofurans; D002791:Cholesterol, Dietary; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D011341:Probucol