Abstract 17007: CCR2 Antagonist Inhibits Neointimal Proliferation Post CoronaryStent Deployment
Background: Using porcine coronary arteries, the efficacy of the novel selective antagonist for CCR2, the receptor for monocyte chemoattractant protein 1, CCX140-B, was evaluated for its ability to inhibit neointimal proliferation following bare metal stent deployment.
Method: 24 bare metal stents were deployed in the coronary arteries of 6 swine (9 in LAD, 6 in LCX, 9 in RCA). The deployed stent length and diameter were the same for each group: diameter 3.2±0.6mm, length 12.8±2.4mm. Two days prior to stent deployment, CCX140 (dissolved in 1ml of 0.9% saline) (treated group, n = 3) or placebo (control group, n = 3) was injected intramuscularly and continued for 28days post stent deployment. The dose of CCX140-B was chosen to achieve >90% receptor coverage (A10) during the course of the experiment. This dosing level resulted in two pigs displaying the expected drug levels at the end of study (A10) while one pig showed lower than expected drug levels (A3). At 28 days post stent deployment several analyses of in-stent restenosis were performed, including coronary angiography, optical coherence tomography (OCT), and intravascular ultrasound (IVUS). The swine were then sacrificed and histological analysis of stented arteries was performed.
Results: Percent neointimal volume obtained by OCT and IVUS was significantly lower in the CCX140-B treatment group with A10 trough drug levels than in the placebo group (29.7±13.7 vs. 43±13.7%, p=0.02). Percent area stenosis obtained by all analytical methods was significantly lower in the CCX140-B treated group with A10 trough drug levels than in the placebo group (27.4±3.4 vs. 39.6±2.8%, p=0.004). Moreover, the stented lumen volume was comparable across all groups (9.4±2.6 vs. 9.3±2.3, p=n.s), indicating that CCX140-B did not work by increasing vessel volume, but through inhibiting neointimal proliferation.
Conclusions: In conclusion, the results of our study suggest that systemic CCR2 antagonism (>90% receptor coverage) by CCX140-B significantly inhibits neointimal proliferation post bare metal stent deployment in a porcine model.
- © 2010 by American Heart Association, Inc.