Cannabinoid-sensitive receptors in cardiac physiology and ischaemia

• Published in: Biochimica et biophysica acta. Molecular cell research 2020-03, Vol.1867 (3), p.118462-118462, Article 118462
• Main Author: Puhl, Sarah-Lena
• Format: Article
• Language: English
• Subjects: Cannabinoids; CB1; CB2; GPR55; Ischaemia/reperfusion; Marijuana; Myocardial infarction
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2019.03.009

The classical cannabinoid receptors CB1 and CB2 as well as the cannabinoid-sensitive receptor GPR55 are widely distributed throughout the mammalian body. In the cardiovascular field, CB1 and CB2 crucially impact on diseases characterized by inflammatory processes, such as atherosclerosis and acute myocardial infarction. Both receptors and their endogenous ligands anandamide and 2-arachidonoylglycerol are up-regulated in the ischaemic heart in humans and animal models. Pharmacological and genetic interventions with CB1 and CB2 vitally affect acute ischaemia-induced cardiac inflammation. Herein, CB1 rather aggravates the inflammatory response whereas CB2 mitigates inflammation via directly affecting immune cell attraction, macrophage polarization and lymphocyte clusters in the pericardial adipose tissue. Furthermore, cannabinoids and their receptors affect numerous cardiac risk factors. In this context, cannabis consumption is debated to trigger arrhythmias and even myocardial infarction. Moreover, CB1 activation is linked to impaired lipid and glucose metabolism and therefore obesity and diabetes, while its antagonism leads to the reduction of plasma triglycerides, low-density lipoprotein cholesterol, leptin, insulin and glucose. On the other hand, activation of cannabinoid-sensitive receptors can also counteract unfavourable predictors for cardiovascular diseases. In particular, hypertension can be mitigated via CB1 agonism and impaired adrenoceptor responsiveness prevented by functional GPR55. Taken together, current insights identify the cannabinoid system as promising target not only to therapeutically interfere with the vasculature, but also to affect the heart as target organ. This review discusses current knowledge regarding a direct cardiac role of the cannabinoid system and points out its feasible therapeutic manipulation in the ischaemic myocardium. •Cannabinoid receptors are up-regulated following cardiac ischaemia•CB2 limits ischaemia-induced neutrophil infiltration and promotes infarct healing•CB1 promotes inflammatory responses triggered by cardiac ischemia•The orphan GPCR GPR55 is sensitive to phyto-, endo- and synthetic cannabinoids•Cardiac effects of synthetic CB1 antagonists may rather result from concurrent GPR55 stimulation