Effect of methylene methylimino linkage of antisense oligonucleotide to the platelet-derived growth factor A-chain on growth of vascular smooth muscle cells from spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells show exaggerated growth and increased expression of platelet-derived growth factor (PDGF) A-chain mRNA. We examined the effect of methylene methylimino linkage of antisense oligodeoxynucleotide, a novel modification of antise...

Full description

Saved in:
Bibliographic Details
Published in:European journal of pharmacology 2000-03, Vol.392 (3), p.129-132
Main Authors: Kishioka, Hirobumi, Fukuda, Noboru, Nakayama, Mari, Hu, Wen-Yang, Satoh, Chikara, Kanmatsuse, Katsuo, Manoharan, Muthiah
Format: Article
Language:English
Subjects:
Alkenes - chemistry
Animals
Antihypertensive agents
Antisense
Biological and medical sciences
Cardiovascular system
Cell Division - drug effects
Cells, Cultured
DNA - biosynthesis
DNA - drug effects
Medical sciences
Methylene methylimino linkage
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - metabolism
Oligonucleotides, Antisense - chemistry
Oligonucleotides, Antisense - metabolism
Oligonucleotides, Antisense - pharmacology
Pharmacology. Drug treatments
Platelet-Derived Growth Factor - antagonists & inhibitors
Platelet-Derived Growth Factor - genetics
Platelet-derived growth factor A-chain
Rats
Rats, Inbred SHR
Single-Strand Specific DNA and RNA Endonucleases - metabolism
Smooth muscle cell
Spontaneously hypertensive rat (SHR)
Thionucleotides - chemistry
Thionucleotides - metabolism
Thionucleotides - pharmacology
vascular
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells show exaggerated growth and increased expression of platelet-derived growth factor (PDGF) A-chain mRNA. We examined the effect of methylene methylimino linkage of antisense oligodeoxynucleotide, a novel modification of antisense oligodeoxynucleotide designed to increase nuclease resistance, to PDGF A-chain on the exaggerated growth of vascular smooth muscle cells from SHR. Methylene methylimino-linked oligodeoxynucleotide provided complete resistance against S1 nuclease. Methylene methylimino linkage of antisense oligodeoxynucleotide to PDGF A-chain resulted in a rapid inhibition of basal DNA synthesis of vascular smooth muscle cells from SHR. This inhibition was much greater than that produced by phosphorothioate linkage of antisense oligodeoxynucleotide to PDGF A-chain. The methylene methylimino linkage of antisense oligodeoxynucleotide to PDGF A-chain may prove useful in the treatment of arterial proliferative diseases including hypertension.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(00)00068-6