Oligodeoxynucleotides directed to early growth response gene-1 mRNA inhibit DNA synthesis in the smooth muscle cell.
Vascular smooth muscle cell proliferation plays a central role in the pathophysiology of cardiovascular diseases. The induction of the early growth response gene-1 (egr-1) mRNA is associated with different cellular processes such as cell proliferation. Antisense oligodeoxynucleotides seem to provide a promising new pharmaceutical tool for effective modification of the expression of specific genes. Hence, in the present study, the effect of 15-mer antisense oligodeoxynucleotides (targeted to the initial codon region of the egr-1 mRNA) on the angiotensin II- and platelet-derived growth factor-BB-induced growth promoting effects of aortic smooth muscle cells was evaluated. Angiotensin II- and platelet-derived growth factor-BB induced egr-1 mRNA (3.4 kb) and Egr-1 protein (80 kDa) in a time- and concentration-dependent fashion. No effects of the sense and antisense oligodeoxynucleotides on the agonist-induced elevation of the egr-1 mRNA and on the Egr-1 protein could be demonstrated. However, they effectively inhibited the angiotensin II- and the platelet-derived growth factor-BB-induced DNA synthesis. Our findings provide evidence that the oligodeoxynucleotides inhibit vascular smooth muscle cell growth via nonantisense mechanism(s).
Sachinidis
A
A
Medizinische Universitäts-Poliklinik, Bonn, Germany.
Schulte
K B
KB
Ko
Y
Y
Seul
C
C
Meyer zu Brickwedde
M K
MK
Düsing
R
R
Vetter
H
H
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D004247:DNA / Q000187:drug effects*; D005260:Female; D017781:Genes, Immediate-Early / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009841:Oligonucleotides / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY
D009841:Oligonucleotides; D000804:Angiotensin II; D004247:DNA