This study sought to investigate whether the endocannabinoid system is involved in human atherosclerosis and whether CB1 receptor antagonism could modulate proinflammatory activity associated with atherogenesis. Direct coronary atherectomy samples of patients with unstable angina had significantly higher levels of CB1 receptor mRNA expression compared to those from patients with stable angina. CB1 receptor expression was greater in lipid-rich atheromatous plaques than in fibrous plaques. Moreover, endocannabinoid concentrations were higher in patients with coronary artery disease than in subjects without coronary artery disease. Finally, CB1 receptor antagonism in macrophages significantly decreased the production of proinflammatory markers such as interleukin-1β, interleukin-6, interleukin-8, matrix metalloproteinase-9, and tumor necrosis factor-a. Patients with coronary artery disease therefore show an overactivity of the endocannabinoid system. These results suggest that antagonism of CB1 receptors might play a protective role in atherogenesis by inhibiting inflammatory processes.
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