Abstract 12051: Cannabinoid Receptor 2 Signaling Does Not Modulate Atherogenesis In Mice
Background:Strong evidence supports a protective role of the cannabinoid receptor 2 (CB2) in inflammation and atherosclerosis. However, direct proof of its involvement in lesion formation is lacking. Therefore, the present study aimed to characterize the role of the CB2 receptor in Murine atherogenesis.
Methods and Results:Low density lipoprotein receptor-deficient (LDLR−/−) mice subjected to intraperitoneal injections of the selective CB2 receptor agonist JWH-133 or vehicle three times per week consumed a high cholesterol diet (HCD) for 16 weeks. Surprisingly, intimal lesion size did not differ between both groups in sections of the aortic roots (0.316±0.038mm2 vs. 0.312±0.044mm2, N≥8, P=0.94) and arches (0.091±0.024mm2 vs. 0.066±0.013mm2, N≥8, P=0.41), suggesting that CB2 activation does not modulate atherogenesis in vivo. Plaque content of lipids, macrophages, smooth muscle cells, T cells, and collagen was also similar in both groups. Accordingly, CB2−/−/LDLR−/− mice developed lesions of similar size in roots (0.261±0.038mm2 vs. 0.223±0.023mm2, N≥12, P=0.40) and arches (0.095±0.022mm2 vs. 0.075±0.022mm2, N≥12, P=0.54) as CB2+/+/LDLR−/− controls consuming HCD for 16 weeks. With exception of an increase in lipid and macrophage content, plaque composition was also similar between these two groups. Neither genetic deficiency nor pharmacologic activation of the CB2 receptor altered inflammatory cytokine expression or peritoneal leukocyte recruitment in vivo or inflammatory cell adhesion in the flow chamber in vitro.
Conclusions:Our study demonstrates that both, activation and deletion of the CB2 receptor do not modulate atherogenesis in mice. Our data do not challenge the multiple reports involving CB2 in other inflammatory processes. However, in the context of atherosclerosis, CB2 does not appear to be a suitable therapeutic target.
- © 2010 by American Heart Association, Inc.