Ezetimibe reduces intimal hyperplasia in rabbit jugular vein graft

Maekawa T, Komori K, Morisaki K, et al (Nagoya Univ Graduate School of Medicine, Japan; et al) J Vasc Surg 56:1689-1697, 2012^§

Abstract

Background

The selective cholesterol transport inhibitor ezetimibe is widely used to prevent development of atherosclerosis in patients with hypercholesterolemia. However, whether this agent inhibits intimal hyperplasia in autologous vein grafts is unknown. The present study was undertaken to clarify if ezetimibe reduces cell proliferation and intimal hyperplasia in vein grafts.

Methods

Forty-four rabbits were randomly divided into two groups: one group received ezetimibe (0.6 mg/kg/d), and the control group did not. Ezetimibe administration was started 1 week before rabbits underwent interposition reversed autologous jugular vein grafts. The proliferative cells and apoptotic cells were counted in the vein grafts 14 days after implantation, and changes in acetylcholine-induced relaxation and endothelial intracellular concentration of Ca²⁺ ([Ca²⁺]_i) were examined at 28 days.

Results

Ezetimibe reduced serum cholesterol and triglyceride. There were fewer proliferating cells in the ezetimibe group (5.7% ± 0.2%, n = 7) than in the control group (12.8% ± 0.5%, n = 7; P < .0001) and more apoptotic cells in the ezetimibe group (5.3% ± 0.2%, n = 7) than in the control group (2.3% ± 0.2%, n = 7; P < .0001). Intimal hyperplasia was less in the ezetimibe group (46.1 ± 6.0 μm, n = 7) than in the control group (76.0 ± 2.5 μm, n = 7; P < .01). Acetylcholine-produced endothelium-dependent relaxation was observed only in the ezetimibe group, which was blocked by the nitric oxide (NO) synthase inhibitor N^ω– nitro-L-arginine. Acetylcholine increased [Ca²⁺]_i only in the ezetimibe group.

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