title: Stent-based delivery of antisense oligodeoxynucleotides targeted to the PDGF A-chain decreases in-stent restenosis of the coronary artery.
abstract: BACKGROUND
  Although the use of drug-eluting stents (DESs) has been shown to limit neointima hyperplasia, currently available DESs may adversely affect reendothelialization, possibly precipitating cardiac events. We evaluated the effect of an antisense oligodeoxynucleotide (ODN) targeted to the platelet-derived growth factor (PDGF) A-chain on in-stent restenosis in pig coronary artery.
  
  
  METHODS
  A bare metal stent coated with phosphorothioate-linked antisense ODN or nonsense ODN, or a bare metal stent without ODN (control), was implanted in the mid segment of the left anterior descending artery (LAD). Twenty-eight days after implantation, angiography and intravascular ultrasound (IVUS) were performed, the LAD was removed, and stenosis was evaluated pathologically.
  
  
  RESULTS
  Volumetric stenosis ratios were 64 +/- 11.9, 44 +/- 3.4, and 26 +/- 3.8% in coronary arteries implanted with control, nonsense ODN-coated, and antisense ODN-coated stents, respectively. In angioscopic findings, the lumen surface was smooth in the stented segments in all groups. Struts of antisense ODN-coated stents were observed embedded in the neointima, whereas embedding was not observed in nonsense ODN-coated stents or control stents, indicating a decrease in hyperplasia in response to antisense ODN treatment. Pathologic findings showed 77 +/- 5.8, 68 +/- 12.2, and 38 +/- 5.3% stenosis in coronary arteries implanted with control stents, nonsense ODN-coated stents, and antisense ODN-coated stents, respectively. A continuous lining of endothelial cells was observed along the lumen of coronary arteries implanted with antisense ODN-coated stents.
  
  
  CONCLUSIONS
  Stent-based delivery of an antisense ODN targeted to the PDGF A-chain effectively inhibits neointima formation after stent implantation in pig coronary artery by suppressing VSMC hyperplasia and preserving endothelialization. Antisense-ODNs may provide a therapy for in-stent restenosis of the coronary artery.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kunimoto
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hagikura
authors.forename: Taro
authors.initials: T
authors.lastname: Kawano
authors.forename: Tadateru
authors.initials: T
authors.lastname: Takayama
authors.forename: Junko
authors.initials: J
authors.lastname: Honye
authors.forename: Naohiko
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Hideo
authors.initials: H
authors.lastname: Mugishima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saito
authors.forename: Kazuo
authors.initials: K
authors.lastname: Serie
mesh_terms: D000818:Animals; D023903:Coronary Restenosis / Q000517:prevention & control*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D015607:Stents; D013552:Swine; D018084:Ultrasonography, Interventional
chemical_list: D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A