Rimonabant, a Selective Cannabinoid CB1 Receptor Antagonist, Inhibits Atherosclerosis in LDL Receptor–Deficient Mice

The objective of this study was to determine whether the potent selective cannabinoid receptor-1 antagonist rimonabant has antiatherosclerotic properties. Rimonabant (50 mg/kg/d in the diet) significantly reduced food intake (from 3.35+/-.04 to 2.80+/-0.03 g/d), weight gain (from 14.6+/-0.7 g to -0.6+/-0.3 g), serum total cholesterol (from 8.39+/-0.54 to 5.32+/-0.18 g/L), and atherosclerotic lesion development in the aorta (from 1.7+/-0.22 to 0.21+/-0.037 mm(2)) and aortic sinus (from 101,000+/-7800 to 27,000+/-2900 microm(2)) of LDLR(-/-) mice fed a Western-type diet for 3 months. Rimonabant also reduced plasma levels of the proinflammatory cytokines MCP-1 and IL12 by 85% (P