Endocannabinoids and the Heart

Endocannabinoids, such as anandamide and 2-arachidonoylglycerol, are synthesized from membrane phospholipids in the heart and other cardiovascular tissues. They activate cannabinoid CB1 and CB2 receptors, transient receptor potential VI (TRPV1), peroxisome proliferator-activated receptors, and perhaps a novel vascular G-protein-coupled receptor. Inactivation is by cellular uptake and fatty acid amide hydrolase.: Endocannabinoids relax coronary and other arteries and decrease cardiac work but seem not to be involved in tonic regulation of cardiovascular function. They act as a stress response system, which is activated, for example, in myocardial infarction and circulatory shock. Endocannabinoids are largely protective; they decrease tissue damage and arrhythmia in myocardial infarction and may reduce progression of atherosclerosis (CB2 receptor stimulation inhibits lesion progression), and fatty acid amide hydrolase knockout mice (which have enhanced endocannabinoid levels) show decreased cardiac dysfunction with age compared with wild types. However, endocannabinoids may mediate doxorubicin-induced cardiac dysfunction. Their signaling pathways are not fully elucidated but they can lead to changed expression of a variety of genes, including those involved in inflammatory responses. There is potential for therapeutic targeting of endocannabinoids and their receptors, but their apparent involvement in both protective and deleterious actions on the heart means that careful risk assessment is needed before any treatment can be introduced.