title: 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.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Nihon University School of Medicine, Ooyaguchi-kami 30-1, Itabashi-ku, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kishioka
authors.forename: N
authors.initials: N
authors.lastname: Fukuda
authors.forename: M
authors.initials: M
authors.lastname: Nakayama
authors.forename: W Y
authors.initials: WY
authors.lastname: Hu
authors.forename: C
authors.initials: C
authors.lastname: Satoh
authors.forename: K
authors.initials: K
authors.lastname: Kanmatsuse
authors.forename: B
authors.initials: B
authors.lastname: Bhat
authors.forename: A M
authors.initials: AM
authors.lastname: Symons
mesh_terms: 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
chemical_list: 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