title: Human placental ectonucleoside triphosphate diphosphohydrolase gene transfer via gelatin-coated stents prevents in-stent thrombosis.
abstract: BACKGROUND
  In-stent thrombosis is mainly triggered by adenosine diphosphate (ADP)-dependent platelet aggregation after percutaneous coronary stent implantation. Ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) rapidly hydrolyzes ADP to adenosine monophosphate, inhibiting platelet aggregation. We tested the hypothesis that local delivery of human placental E-NTPDase (pE-NTPDase) gene into injured arteries via gene-eluting stent could prevent subacute in-stent thrombosis.
  
  
  RESULTS
  We generated gene-eluting stents by coating bare metal stents with cationic gelatin hydrogel containing pE-NTPDase cDNA (pE-NTPDase stent), and implanted the stents into rabbit femoral arteries (FA) prone to production of platelet-rich thrombi due to repeated balloon injury at 4-week intervals. After the second injury, E-NTPDase gene expression was severely decreased; however, the implantation of pE-NTPDase stent increased E-NTPDase mRNA levels and NTPDase activity to higher level than normal FA. The FAs with pE-NTPDase stents maintained patency in all rabbits (P<0.01), whereas the stent-implanted FAs without pE-NTPDase gene showed low patency rates (17% to 25%). The occlusive platelet-rich thrombi, excessive neointimal growth, and infiltration of macrophages were inhibited in stent implanted FA with pE-NTPDase gene, but not without pE-NTPDase gene.
  
  
  CONCLUSIONS
  Human pE-NTPDase gene transfer via cationic gelatin-coated stents inhibited subacute in-stent thrombosis and suppressed neointimal hyperplasia and inflammation without antiplatelet drugs.
authors.affiliation: First Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawata
authors.forename: Tsunenari
authors.initials: T
authors.lastname: Soeda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Imagawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Somekawa
authors.forename: Yukiji
authors.initials: Y
authors.lastname: Takeda
authors.forename: Shiro
authors.initials: S
authors.lastname: Uemura
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Jo
authors.forename: Yu
authors.initials: Y
authors.lastname: Kimura
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito