Abstract 14216: CBP Silencing with Lentivirus Attenuates Neointimal Formation and Promotes Re-endothelialization in Balloon Injured Rat Carotid Artery
Background: Lentiviral vectors provide a promising strategy for the treatment of cardiovascular diseases, owing to their ability to govern efficient and durable gene transfer. However, relatively few studies have been addressed on restenosis after balloon or stent associated arterial injury. CREB binding protein (CBP), a powerful transcriptional coactivator, has recently been reported to regulate cell behavior in vascular endothelial and smooth muscle cells. Therefore, we examined whether inhibition of CBP by lentivirus-mediated small interfering RNA can reduce neointimal formation and accelerate re-endothelialization after arterial injury.
Methods and results: To deliver RNA interference in a rat model of carotid artery balloon injury, lentiviral vectors encoding for a short hairpin RNA against CBP or control were constructed. The carotid arteries from Sprague-Dawley rats were injured by balloon catheter, followed incubated with 100 μl lentivirus or PBS solution for 30 minutes. The rats were euthanized at 4 weeks after operation, and the tissues were harvested for specific protocols. Lentiviral shRNA targeting CBP markedly suppressed CBP mRNA and protein expression induced by balloon injury. Compared with controls (figure 1, P<0.05). Interestingly, endothelial cell marker CD31 immunostaining and Evans blue analysis both showed that CBP silencing significantly accelerated re-endothelialization (P<0.05).
Conclusion: Lentivirus-mediated RNAi targeting CBP attenuates neointimal formation and promotes re-endothelialization in balloon injured rat carotid artery. Ongoing studies are addressing the underlying mechanism(s).
- © 2010 by American Heart Association, Inc.