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The endocannabinoid system in cardiovascular function: novel insights and clinical implications

Abstract

Rationale

Cardiovascular disease is now recognized as the number one cause of death in the world, and the size of the population at risk continues to increase rapidly. The dysregulation of the endocannabinoid (eCB) system plays a central role in a wide variety of conditions including cardiovascular disorders. Cannabinoid receptors, their endogenous ligands, as well as enzymes conferring their synthesis and degradation, exhibit overlapping distributions in the cardiovascular system. Furthermore, the pharmacological manipulation of the eCB system has effects on blood pressure, cardiac contractility, and endothelial vasomotor control. Growing evidence from animal studies supports the significance of the eCB system in cardiovascular disorders.

Objective

To summarize the literature surrounding the eCB system in cardiovascular function and disease and the new compounds that may potentially extend the range of available interventions.

Results

Drugs targeting CB1R, CB2R, TRPV1 and PPARs are proven effective in animal models mimicking cardiovascular disorders such as hypertension, atherosclerosis and myocardial infarction. Despite the setback of two clinical trials that exhibited unexpected harmful side-effects, preclinical studies are accelerating the development of more selective drugs with promising results devoid of adverse effects.

Conclusion

Over the last years, increasing evidence from basic and clinical research supports the role of the eCB system in cardiovascular function. Whereas new discoveries are paving the way for the identification of novel drugs and therapeutic targets, the close cooperation of researchers, clinicians and pharmaceutical companies is needed to achieve successful outcomes.

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Acknowledgements

We thank Jill K Gregory, MFA, CMI for designing illustrations and Dr. Guillermo Sánchez-Elvira for critical reading of the manuscript.

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Correspondence to Salvador Sierra.

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S.S. salary is supported by a Grant from Alfonso Martín Escudero Foundation.

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Sierra, S., Luquin, N. & Navarro-Otano, J. The endocannabinoid system in cardiovascular function: novel insights and clinical implications. Clin Auton Res 28, 35–52 (2018). https://doi.org/10.1007/s10286-017-0488-5

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Keywords

  • Cannabinoid system
  • Cardiovascular disease
  • CB1 receptor
  • CB2 receptor
  • TRPV1
  • PPAR
  • Hypertension
  • Myocardial infarction
  • Atherosclerosis