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Arteriosclerosis, Thrombosis, and Vascular Biology current issue

[Editorials] Arteriosclerosis, Thrombosis, and Vascular Biology, 2009
Taubman, M. Wed, 17 Dec 2008 00:00:00 -0000

[Acknowledgment of Reviewers] Acknowledgment of Reviewers
Wed, 17 Dec 2008 00:00:00 -0000

[Editorials] Carotid Plaque Stabilization and Progression After Stroke or TIA
Virmani, R., Finn, A. V., Kolodgie, F. D. Wed, 17 Dec 2008 00:00:00 -0000

[Editorials] Cannabinoid CB1 Receptor Antagonists for Atherosclerosis and Cardiometabolic Disorders: New Hopes, Old Concerns?
Pacher, P. Wed, 17 Dec 2008 00:00:00 -0000

[Editorials] Vascular Remodeling in Diabetes: Don't Leave Without Your STAT5
Zampetaki, A., Xu, Q. Wed, 17 Dec 2008 00:00:00 -0000

[Integrative Physiology/Experimental Medicine] Rimonabant, a Selective Cannabinoid CB1 Receptor Antagonist, Inhibits Atherosclerosis in LDL Receptor-Deficient Mice
Dol-Gleizes, F., Paumelle, R., Visentin, V., Mares, A.-M., Desitter, P., Hennuyer, N., Gilde, A., Staels, B., Schaeffer, P., Bono, F. Wed, 17 Dec 2008 00:00:00 -0000
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/kg/d in the diet) reduced atherosclerosis development in the aortic sinus (from 121 000±20 000 to 62 000±11 000 µm2, 49% reduction, P<0.05), without affecting serum total cholesterol (7.8±0.7 g/L versus 8.1±1.3 g/L in the control group). Rimonabant decreased lipopolysaccharide (LPS)- and IL1β-induced proinflammatory gene expression in mouse peritoneal macrophages in vitro as well as thioglycollate-induced recruitment of macrophages in vivo (10 mg/kg, po bolus). Conclusions— These results show that rimonabant has antiatherosclerotic effects in LDLR–/– mice. These effects are partly unrelated to serum cholesterol modulation and could be related to an antiinflammatory effect.

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