Objective: To investigate the effects of montelukast on atherosclerosis and monocyte chemoattractant protein-1 expression in a hypercholesterolemic rabbit model.
Methods: Thirty four male New Zealand white rabbits were randomized into four groups including normal control group (n = 6), placebo group (n = 8), atorvastatin group (1.5 mgxkg(-1)xd(-1), beginning at 8(th) weeks for 4 weeks, n = 10) and montelukast group (1 mgxkg(-1)xd(-1), beginning at 8(th) weeks for 4 weeks, n = 10). Rabbits except those in normal control group were fed a high cholesterol diet for 12 weeks. Serum lipids were measured at 0, 8 and 12 weeks after intervention. The intima/media ratio, percentages of macrophages or smooth muscle cells in intima and the expression of MCP-1 mRNA were examined.
Results: Atherosclerosis was evidenced in placebo group and atorvastatin or montelukast treatment significantly reduced neointima (0.32 +/- 0.12 and 0.34 +/- 0.10 vs. 1.12 +/- 0.36, P < 0.05) and macrophage content [(9.8 +/- 4.6)% and (11.2 +/- 3.7)% vs. (34.6 +/- 8.8)%, P < 0.05], increased SMC content [(18.6 +/- 6.9)% and (19.2 +/- 8.6)% vs. (5.2 +/- 2.3)%, P < 0.05] and inhibited expression of MCP-1 mRNA (0.42 +/- 0.08 and 0.40 +/- 0.06 vs. 2.36 +/- 0.48, P < 0.01). Montelukast had similar anti-atherogenetic effects as atorvastatin but had no influence on plasma lipids.
Conclusions: Montelukast could attenuate atherosclerosis in this hypercholesterolemic rabbit model which might be attributed to its anti-inflammatory effects.