Anti-atherogenic effects of montelukast associated with reduced MCP-1 expression in a rabbit carotid balloon injury model

Atherosclerosis is characterized by inflammatory responses of the arterial wail to injury, which is prominently driven by inflammatory mediators. Montelukast, a selective CysLT1 receptor antagonist, has potent anti-inflammatory effects in diverse animal models. However, the role of montelukast in regulating inflammatory progression of atherosclerosis has not been elucidated. Therefore, we investigated the effect of montelukast on atherosclerosis compared with that of atorvastatin. Twenty-six male New Zealand White rabbits were randomized into four groups including a negative control group. The rabbits were fed a normal diet or an atherogenic diet for 12 weeks. The rabbits, except the negative control group, received right carotid artery balloon-injury 2 weeks after initiation of the atherogenic diet. Animals were then treated with montelukast (1 mg/kg/day), atorvastatin (1.5 mg/kg/day) or placebo for 4 weeks, respectively. At the end of the treatment, animals were killed and carotids were dislodged and detected. The results indicated that the placebo group had significant progression of atherosclerosis compared with the negative control group. In contrast, montelukast or atorvastatin treated rabbits showed a significant reduction of neointima, decreased macrophage content, increased SMC content and inhibited expression of MCP-1. Between two drugs, there were no significant differences in reducing neointima and decreasing the level of MCP-1. However, montelukast had no influence on plasma lipids, while atorvastatin down-regulated the levels of TC, TG and LDL These results suggest that montelukast produces anti-atherogenic effects unrelated to plasma lipid modulation but related to MCP-1 down regulation. (C) 2008 Elsevier Ireland Ltd. All rights reserved.