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 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.
Kishioka
H
H
Second Department of Internal Medicine, Nihon University School of Medicine, Ooyaguchi-kami 30-1, Itabashi-ku, Tokyo, Japan.
Fukuda
N
N
Nakayama
M
M
Hu
W Y
WY
Satoh
C
C
Kanmatsuse
K
K
Bhat
B
B
Symons
A M
AM
D000475:Alkenes / Q000737:chemistry; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D013873:Thionucleotides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D000475:Alkenes; D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D013873:Thionucleotides; C075278:platelet-derived growth factor A; D004247:DNA; D015719:Single-Strand Specific DNA and RNA Endonucleases