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.


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+/-6% 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 microm; 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.
Tanous
David
D
Centre for Vascular Research, School of Medical Sciences, University of New South Wales and Department of Haematology, Prince of Wales Hospital, Sydney, Australia.
Bräsen
Jan Hinrich
JH
Choy
Katherine
K
Wu
Ben J
BJ
Kathir
Krishna
K
Lau
Antony
A
Celermajer
David S
DS
Stocker
Roland
R
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000517:prevention & control*; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D007083:Iliac Artery / Q000473:pathology / Q000601:surgery; D007150:Immunohistochemistry; D008297:Male; D011341:Probucol / Q000627:therapeutic use*; D011817:Rabbits; D015607:Stents; D013927:Thrombosis / Q000473:pathology / Q000517:prevention & control*; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
D000975:Antioxidants; D011341:Probucol