title: Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages.
abstract: The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer. However, its physiological role and underlying mechanism remain unclear. In the present work, we demonstrate for the first time its presence in human macrophages and its increased expression in ox-LDL-induced foam cells. In addition, pharmacological activation of GPR55 by its selective agonist O-1602 increased CD36- and SRB-I-mediated lipid accumulation and blocked cholesterol efflux by downregulating ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, as well as enhanced cytokine- and pro-metalloprotease-9 (pro-MMP-9)-induced proinflammatory responses in foam cells. Treatment with cannabidiol, a selective antagonist of GPR55, counteracted these pro-atherogenic and proinflammatory O-1602-mediated effects. Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases.
authors.affiliation: European Center for Brain Research (CERC), IRCCS, Santa Lucia Foundation, Rome, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Lanuti
authors.affiliation: European Center for Brain Research (CERC), IRCCS, Santa Lucia Foundation, Rome, Italy; Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Talamonti
authors.affiliation: European Center for Brain Research (CERC), IRCCS, Santa Lucia Foundation, Rome, Italy; Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
authors.affiliation: European Center for Brain Research (CERC), IRCCS, Santa Lucia Foundation, Rome, Italy; Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Chiurchiù
mesh_terms: D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism; D002185:Cannabidiol / Q000031:analogs & derivatives; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D003510:Cyclohexanes / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005487:Foam Cells / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology
chemical_list: D003510:Cyclohexanes; D016207:Cytokines; C524885:GPR55 protein, human; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D050778:NFATC Transcription Factors; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled; D012118:Resorcinols; C099252:oxidized low density lipoprotein; D002185:Cannabidiol; C568537:O-1602 compound; D002784:Cholesterol; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9