Review

Subject Category: Review Article

British Journal of Pharmacology (2008) 153, 290–298; doi:10.1038/sj.bjp.0707517; published online 29 October 2007

Cannabinoid receptors in acute and chronic complications of atherosclerosis

F Mach1, F Montecucco1 and S Steffens1

1Department of Internal Medicine, Division of Cardiology, Geneva University Hospital, Foundation for Medical Researches, Geneva, Switzerland

Correspondence: Dr S Steffens, Department of Internal Medicine, Division of Cardiology, Geneva University Hospital, Foundation for Medical Researches, 64 Avenue Roseraie, Geneva 1211, Switzerland. E-mail: sabine.steffens@medecine.unige.ch

Received 2 July 2007; Revised 21 September 2007; Accepted 28 September 2007; Published online 29 October 2007.

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Abstract

Atherosclerosis is a chronic inflammatory disease that is the primary cause of myocardial infarction and stroke, which occur after sudden thrombotic occlusion of an artery. A growing body of evidence suggests that cannabinoid signalling plays a fundamental role in atherosclerosis development and its clinical manifestations. Thus, CB2 receptors are protective in myocardial ischaemia/reperfusion and implicated in the modulation of chemotaxis, which is crucial for the recruitment of leukocytes during inflammation. Delta-9-Tetrahydrocannabinol (THC)-mediated activation has been shown to inhibit atherosclerotic plaque progression in a CB2 dependent manner. Although CB1 and CB2 expression has been reported on platelets, their involvement in thrombus formation is still controversial. While several reports suggest that CB1 receptors may have a relevant role in neuroprotection after ischaemic stroke, recent studies show the protective effects in various forms of neuroprotection are not related to CB1 stimulation, and a protective role of CB1 blockade has also been reported. In addition, vascular and myocardial CB1 receptors contribute to the modulation of blood pressure and heart rate. It is tempting to suggest that pharmacological modulation of the endocannabinoid system is a potential novel therapeutic strategy in the treatment of atherosclerosis. For these purposes, it is important to better understand the complex mechanisms of endocannabinoid signalling and potential consequences of its pharmacological modulation, as it may have both pro- and anti-atherosclerotic effects.

Keywords:

atherosclerosis, inflammation, myocardial infarction, stroke, post-ischaemic heart failure, remodelling, cannabinoid receptors, cannabinoids

Abbreviations:

ICAM-1, intercellular adhesion molecule-1; I/R, ischaemia/reperfusion; THC, delta-9-tetrahydrocannabinol

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