Abstract
A recent clinical study using coronary intravascular ultrasound showed that rimonabant, a cannabinoid 1 (CB1) receptor antagonist, significantly reduced total atheroma volume, suggesting that CB1 receptor blockade could be beneficial in anti-atherogenic therapy. The reverse cholesterol transport (RCT) system plays important roles in atherogenesis. We investigated whether CB1 receptor blockade could modulate atherogenesis in mice. Oral administration of rimonabant (8 mg/kg/day) to apolipoprotein E-deficient mice for 3 months significantly reduced the relative area of atherosclerotic lesions in the aorta (vehicle; 12.6+/-4.0% vs. rimonabant; 9.7+/-2.3, n=12 each, p<0.05) with an increase in serum adiponectin levels (15.6+/-2.3 microg/mL vs. 12.2+/-2.1, n=12 each, p<0.001), without affecting body weight or serum cholesterol levels. Rimonabant tended to increase serum high-density lipoprotein cholesterol (HDL-C) (p=0.05). The relative area of atherosclerotic lesions in the aorta correlated inversely with serum HDL-C levels (r=-0.45, n=24, p<0.05). Rimonabant upregulated the mRNA expression levels of various components of the RCT system on THP-1 cell-derived macrophages (scavenger receptor B1: 1.15+/-0.12 fold, n=6; p<0.05, ATP-bind...Continue Reading
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