The nucleotide analogue 3-deazaadenosine prevents neointima-formation after balloon injury.
We have recently shown that 3-deazaadenosine (c3Ado) inhibits atherogenesis in mice. We studied whether its anti-inflammatory capacity would also affect neointima-formation after balloon injury. Sprague Dawley rats underwent balloon angioplasty. C3Ado was administered orally, starting 5 days prior to the balloon injury and continued for 2 weeks. Fourteen days after balloon injury the intima/media ratio in the c3Ado-treated group was reduced by 67% (p<0.001) and luminal stenosis by 50% (p<0.001). Neointimal cellular density was decreased by 25% (p<0.001) and the induction of c-Jun and ki67 was markedly lower. The reduction of the intima/media ratio was still observed 3 months after balloon injury. Furthermore, a c3Ado-dependent inhibition of PDGF-mediated ERK-activation and proliferation could be demonstrated. Short-term administration of C3Ado inhibits neointima-formation in rats for at least 3 months after injury. The present findings implicate that c3Ado may be useful as an inhibitor of restenosis-formation after balloon angioplasty in humans.
Seeger
Florian H
FH
Zentrum für Innere Medizin, Kardiologie, Universität Frankfurt, Frankfurt am Main, Germany.
Hess
Wolfram
W
Sedding
Daniel
D
Becker
Gunter
G
Kinscherf
Ralf
R
Braun-Dullaeus
Ruediger C
RC
Viedt
Christiane
C
Kreuzer
Jörg
J
D000284:Administration, Oral; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D023903:Coronary Restenosis / Q000473:pathology / Q000517:prevention & control*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014372:Tubercidin / Q000008:administration & dosage* / Q000009:adverse effects; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries / Q000473:pathology
C018258:3-deazaadenosine; D048049:Extracellular Signal-Regulated MAP Kinases; D014372:Tubercidin