Stent-based delivery of antisense oligodeoxynucleotides targeted to the PDGF A-chain decreases in-stent restenosis of the coronary artery.
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.
Li
Yuxin
Y
Department of Medicine, Division of Cardiovascular Medicine, Nihon University School of Medicine, Tokyo, Japan.
Fukuda
Noboru
N
Kunimoto
Satoshi
S
Yokoyama
Shin-ichiro
S
Hagikura
Kazuhiro
K
Kawano
Taro
T
Takayama
Tadateru
T
Honye
Junko
J
Kobayashi
Naohiko
N
Mugishima
Hideo
H
Saito
Satoshi
S
Serie
Kazuo
K
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
D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A