Endocannabinoid signalling as an anti-inflammatory therapeutic target in atherosclerosis: does it work?

The endocannabinoid system is a physiological signalling network that has attracted major attention in recent years because of its therapeutic potential for the treatment of various pathological conditions, including cardiovascular disease. More specifically, targeted modulation of the major receptors of this system, the G-protein-coupled cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors, has been implicated in the protection against atherosclerosis. Accumulating evidence suggests that specific blockage of these receptors may have beneficial effects on classical cardiovascular risk factors such as hypercholesterolaemia, obesity, and impaired glucose tolerance.1 In a pioneering report, it was demonstrated that low levels of the cannabinoid derivative delta-9-tetrahydrocannabinoid reduced the progression of atherosclerosis in an apolipoprotein E knockout mouse model of established atherosclerosis via the CB2 receptor. This protective effect has been shown to be mediated via the immunomodulatory, anti-inflammatory actions of this receptor.2 Subsequently, CB2 receptor-dependent anti-inflammatory therapeutic effects have also been observed in other conditions such as sepsis.3 More recently, the CB1 receptor antagonist rimonabant (SR141716) has been shown to provide anti-inflammatory protection against atherosclerosis.4 Since the majority of these studies have been performed in mouse models, the relevance of the findings for humans has remained largely elusive. Moreover, the regulatory role of cannabinoid signalling for specific interactions of immune cells with the vascular system … *Corresponding author. Tel: +49 511 532 6704/9714; fax: +49 511 532 2079. E-mail address : immenschuh.stephan{at}mh-hannover.de