title: Cannabinoid 1 receptor blockade reduces atherosclerosis with enhances reverse cholesterol transport.
abstract: OBJECTIVE
  A recent clinical study using coronary intravascular ultrasound showed that rimonabant, a cannabinoid 1 (CB1) receptor antagonist, significantly reduced total atheroma volume, suggesting that CB1 receptor blockade could be beneficial in anti-atherogenic therapy. The reverse cholesterol transport (RCT) system plays important roles in atherogenesis. We investigated whether CB1 receptor blockade could modulate atherogenesis in mice.
  
  
  RESULTS
  Oral administration of rimonabant (8 mg/kg/day) to apolipoprotein E-deficient mice for 3 months significantly reduced the relative area of atherosclerotic lesions in the aorta (vehicle; 12.6+/-4.0% vs. rimonabant; 9.7+/-2.3, n=12 each, p<0.05) with an increase in serum adiponectin levels (15.6+/-2.3 microg/mL vs. 12.2+/-2.1, n=12 each, p<0.001), without affecting body weight or serum cholesterol levels. Rimonabant tended to increase serum high-density lipoprotein cholesterol (HDL-C) (p=0.05). The relative area of atherosclerotic lesions in the aorta correlated inversely with serum HDL-C levels (r=-0.45, n=24, p<0.05). Rimonabant upregulated the mRNA expression levels of various components of the RCT system on THP-1 cell-derived macrophages (scavenger receptor B1: 1.15+/-0.12 fold, n=6; p<0.05, ATP-binding cassette [ABC] transporter G1: 1.23+/-0.11 fold, n=6; p<0.01), but not ABCA1 (1.13+/-0.20 fold, n=6; p=0.13).
  
  
  CONCLUSIONS
  CB1 receptor blockade reduced atherosclerosis in apoE-deficient mice through an increase in serum adiponectin levels and activation of the RCT system. CB1 receptor blockade may be therapeutically beneficial for atherogenesis by increasing the serum adiponectin level and enhancing of the RCT system.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sugamura
authors.forename: Seigo
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Junichi
authors.initials: J
authors.lastname: Matsubara
authors.forename: Eiichi
authors.initials: E
authors.lastname: Akiyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Maeda
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohba
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Konishi
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Nozaki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Horibata
authors.forename: Koichi
authors.initials: K
authors.lastname: Kaikita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sumida
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D052242:Adiponectin; D000284:Administration, Oral; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010880:Piperidines / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage*; D043882:Receptors, Cannabinoid / Q000235:genetics* / Q000378:metabolism; D000077285:Rimonabant
chemical_list: D052242:Adiponectin; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D002784:Cholesterol; D000077285:Rimonabant