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

Objective— The objective of this study was to determine whether the potent selective cannabinoid receptor-1 antagonist rimonabant has antiatherosclerotic properties. Methods and Results— 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 mm2) and aortic sinus (from 101 000±7800 to 27 000±2900 μm2) 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<0.05) and 76% (P<0.05), respectively. Pair-fed animals had reduced weight gain (6.2±0.6 g gain), but developed atherosclerotic lesions which were as large as those of untreated animals, showing that the antiatherosclerotic effect of rimonabant is not related to reduced food intake. Interestingly, rimonabant at a lower dose (30 mg/k...