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The emerging role of the endocannabinoid system in cardiovascular disease

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Abstract

Endocannabinoids are endogenous bioactive lipid mediators present both in the brain and various peripheral tissues, which exert their biological effects via interaction with specific G-protein-coupled cannabinoid receptors, the CB1 and CB2. Pathological overactivation of the endocannabinoid system (ECS) in various forms of shock and heart failure may contribute to the underlying pathology and cardiodepressive state by the activation of the cardiovascular CB1 receptors. Furthermore, tonic activation of CB1 receptors by endocannabinoids has also been implicated in the development of various cardiovascular risk factors in obesity/metabolic syndrome and diabetes, such as plasma lipid alterations, abdominal obesity, hepatic steatosis, inflammation, and insulin and leptin resistance. In contrast, activation of CB2 receptors in immune cells exerts various immunomodulatory effects, and the CB2 receptors in endothelial and inflammatory cells appear to limit the endothelial inflammatory response, chemotaxis, and inflammatory cell adhesion and activation in atherosclerosis and reperfusion injury. Here, we will overview the cardiovascular actions of endocannabinoids and the growing body of evidence implicating the dysregulation of the ECS in a variety of cardiovascular diseases. We will also discuss the therapeutic potential of the modulation of the ECS by selective agonists/antagonists in various cardiovascular disorders associated with inflammation and tissue injury, ranging from myocardial infarction and heart failure to atherosclerosis and cardiometabolic disorders.

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Acknowledgements

S.S. is supported by grants from the Swiss National Science Foundation, the Novartis Foundation for Biomedical Research, Prevot and Wolfermann-Naegeli Foundation. P.P. is supported by the Intramural research program of the NIH/NIAAA.

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Authors and Affiliations

  1. Section on Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, National Institutes of Health/NIAAA, 5625 Fishers Lane, MSC-9413, Bethesda, MD, 20892-9413, USA

    Pál Pacher

  2. Division of Cardiology, Department of Internal Medicine, University Hospital, Foundation for Medical Researches, Avenue Roseraie 64, 1211, Geneva, Switzerland

    Sabine Steffens

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  1. Pál Pacher
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Correspondence to Pál Pacher or Sabine Steffens.

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Pacher, P., Steffens, S. The emerging role of the endocannabinoid system in cardiovascular disease. Semin Immunopathol 31, 63–77 (2009). https://doi.org/10.1007/s00281-009-0145-8

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