The Role of the Endocannabinoid System in Atherosclerosis.

Our current understanding of the pathophysiology of atherosclerosis suggests a prominent role for immune responses from its initiation through its complications. Given the increasing prevalence of cardiovascular risk factors worldwide, there is an urgent need to better understand the underlying mechanisms to improve current treatment protocols. A growing body of evidence suggests that endocannabinoid signalling plays a critical role in the pathogenesis of atherogenesis and its clinical manifestations. Blocking CB₁ receptors has been shown to mediate not only weight reduction, but also several cardiometabolic effects in rodents and humans, indicating a potential relevance for the process of atherosclerosis. Activation of CB₂ receptors with Δ⁹-tetrahydrocannabinol (THC) has been shown to inhibit atherosclerotic plaque progression in mice, mainly by inhibiting macrophage recruitment. Endocannabinoids released from endothelial cells, macrophages or platelets, reduce hypertension in rodents, a major risk factor for atherosclerosis. In addition, anandamide inhibits inflammatory gene expression in endothelial cells, and consequently monocyte adhesion. Conversely, endocannabinoids might also mediate pro-atherosclerotic effects by inducing platelet activation. In conclusion, the precise role of the endocannabinoid system during atherosclerosis is not yet understood. Whether increased endocannabinoid signalling is associated with disease progression and increased risk of acute thrombotic events remains to be determined. [ABSTRACT FROM AUTHOR]