Salvador Sierra1,2, Natasha Luquin3, Judith Navarro-Otano4. 1. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Salvador.Sierra@vcuhealth.org. 2. Department of Physiology and Biophysics, Molecular Medicine Research Building, Virginia Commonwealth University, 1220 East Broad Street, Richmond, VA, 23298, USA. Salvador.Sierra@vcuhealth.org. 3. Department of Medical Genomics, Royal Prince Alfred Hospital, Sydney, Australia. 4. Neurology Service, Electromyography, Motor Control and Neuropathic Pain Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
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.
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.
Authors: Marta Toral; Miguel Romero; Francisco Pérez-Vizcaíno; Juan Duarte; Rosario Jiménez Journal: Am J Physiol Heart Circ Physiol Date: 2016-11-23 Impact factor: 5.125
Authors: Carlos Hernández-Díaz; Marco Antonio Juárez-Oropeza; Dieter Mascher; Natalia Pavón; Ignacio Regla; María Cristina Paredes-Carbajal Journal: Cannabis Cannabinoid Res Date: 2020-02-27