Decades of research has provided evidence for the role of the endocannabinoid system in
human health and disease. This versatile system, consisting of two receptors (CB1 and CB2), their
endogenous ligands (endocannabinoids), and metabolic enzymes has been implicated in a wide
variety of disease states, ranging from neurological disorders to cancer. CB2 has gained much
interest for its beneficial immunomodulatory role that can be obtained without eliciting psychotropic
effects through CB1. Recent studies have shed light on a protective role of CB2 in cardiovascular
disease, an ailment which currently takes more lives each year in Western countries than any other
disease or injury. By use of CB2 knockout mice and CB2-selective ligands, knowledge of how CB2
signaling affects atherosclerosis and ischemia has been acquired, providing a major stepping stone
between basic science and translational clinical research. Here, we summarize the current
understanding of the endocannabinoid system in human pathologies and provide a review of the
results from preclinical studies examining its function in cardiovascular disease, with a particular
emphasis on possible CB2-targeted therapeutic interventions to alleviate atherosclerosis.
Keywords: Cannabinoids, CB1, CB2, atherosclerosis, ischemia/reperfusion, 2-AG, AEA.
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