title: Cannabinoid receptor 2 signaling does not modulate atherogenesis in mice.
abstract: BACKGROUND
  Strong evidence supports a protective role of the cannabinoid receptor 2 (CB(2)) in inflammation and atherosclerosis. However, direct proof of its involvement in lesion formation is lacking. Therefore, the present study aimed to characterize the role of the CB(2) receptor in Murine atherogenesis.
  
  
  RESULTS
  Low density lipoprotein receptor-deficient (LDLR(-/-)) mice subjected to intraperitoneal injections of the selective CB(2) receptor agonist JWH-133 or vehicle three times per week consumed high cholesterol diet (HCD) for 16 weeks. Surprisingly, intimal lesion size did not differ between both groups in sections of the aortic roots and arches, suggesting that CB(2) activation does not modulate atherogenesis in vivo. Plaque content of lipids, macrophages, smooth muscle cells, T cells, and collagen were also similar between both groups. Moreover, CB(2) (-/-)/LDLR(-/-) mice developed lesions of similar size containing more macrophages and lipids but similar amounts of smooth muscle cells and collagen fibers compared with CB(2) (+/+)/LDLR(-/-) controls. While JWH-133 treatment reduced intraperitoneal macrophage accumulation in thioglycollate-elicited peritonitis, neither genetic deficiency nor pharmacologic activation of the CB(2) receptor altered inflammatory cytokine expression in vivo or inflammatory cell adhesion in the flow chamber in vitro.
  
  
  CONCLUSIONS
  Our study demonstrates that both activation and deletion of the CB(2) receptor do not relevantly modulate atherogenesis in mice. Our data do not challenge the multiple reports involving CB(2) in other inflammatory processes. However, in the context of atherosclerosis, CB(2) does not appear to be a suitable therapeutic target for reduction of the atherosclerotic plaque.
authors.affiliation: Department of Cardiology, University of Freiburg, Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Willecke
authors.forename: Katharina
authors.initials: K
authors.lastname: Zeschky
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ortiz Rodriguez
authors.forename: Christian
authors.initials: C
authors.lastname: Colberg
authors.forename: Volker
authors.initials: V
authors.lastname: Auwärter
authors.forename: Stefan
authors.initials: S
authors.lastname: Kneisel
authors.forename: Melanie
authors.initials: M
authors.lastname: Hutter
authors.forename: Andrey
authors.initials: A
authors.lastname: Lozhkin
authors.forename: Natalie
authors.initials: N
authors.lastname: Hoppe
authors.forename: Dennis
authors.initials: D
authors.lastname: Wolf
authors.forename: Constantin
authors.initials: C
authors.lastname: von zur Mühlen
authors.forename: Martin
authors.initials: M
authors.lastname: Moser
authors.forename: Ingo
authors.initials: I
authors.lastname: Hilgendorf
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Andreas
authors.initials: A
authors.lastname: Zirlik
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D002186:Cannabinoids / Q000493:pharmacokinetics / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005247:Feeding Behavior / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002186:Cannabinoids; D016207:Cytokines; D043885:Receptor, Cannabinoid, CB2; D018799:Intercellular Adhesion Molecule-1; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC