Probucol inhibits in-stent thrombosis and neointimal hyperplasia by promoting re-endothelialization

Background: Evidence suggests that delayed re-endothelialization is responsible for in-stent thrombosis. Probucol inhibits neointimal thickening in animals via enhanced re-endothelialization and is the only oral drug that consistently inhibits restenosis after coronary angioplasty in humans. Here, we examined the effects of probucol on re-endothelialization and neointimal formation in a stent model. Methods and results: New Zealand White rabbits were fed a hypercholesterolemic diet with probucol (1%) or without (control) (n = 11 each) for 6 weeks. At 2 weeks, endothelial denudation and stenting of the iliac artery was performed. Iliac arteries were harvested at week 6, and stented segments sectioned and analyzed. Compared with control, probucol increased in-stent re-endothelialization (74 +/- 16% in controls versus 93 +/- 3% in probucol-treated; P = 0.008), and decreased average luminal stenosis (58 +/- 27 versus 31 +/- 16%; P = 0.01) and stent depth (619 +/- 310 versus 314 +/- 158 mu m; P = 0.009). Compared with control, probucol also decreased accumulation of macrophages in the neointima. Furthermore, none of the probucol-treated rabbits had in-stent thrombosis, whereas four of eleven control rabbits showed thrombosis (P = 0.04). Conclusions: Probucol demonstrates anti-restenotic and appears to have anti-thrombotic properties that are likely related to its ability to promote in-stent re-endothelialization. (c) 2006 Elsevier Ireland Ltd. All rights reserved.