title: Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice.
abstract: BACKGROUND
  Dysregulation of adipocyte-derived bioactive molecules plays an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipocyte-specific plasma protein, accumulated in the injured artery from the plasma and suppressed endothelial inflammatory response and vascular smooth muscle cell proliferation, as well as macrophage-to-foam cell transformation in vitro. The current study investigated whether the increased plasma adiponectin could actually reduce atherosclerosis in vivo.
  
  
  RESULTS
  Apolipoprotein E-deficient mice were treated with recombinant adenovirus expressing human adiponectin (Ad-APN) or beta-galactosidase (Ad-betagal). The plasma adiponectin levels in Ad-APN-treated mice increased 48 times as much as those in Ad-betagal treated mice. On the 14th day after injection, the lesion formation in aortic sinus was inhibited in Ad-APN-treated mice by 30% compared with Ad-betagal-treated mice (P<0.05). In the lesions of Ad-APN-treated mice, the lipid droplets became smaller compared with Ad-betagal-treated mice (P<0.01). Immunohistochemical analyses demonstrated that the adenovirus-mediated adiponectin migrate to foam cells in the fatty streak lesions. The real-time quantitative polymerase chain reaction revealed that Ad-APN treatment significantly suppressed the mRNA levels of vascular cell adhesion molecule-1 by 29% and class A scavenger receptor by 34%, and tended to reduce levels of tumor necrosis factor-alpha without affecting those of CD36 in the aortic tissue.
  
  
  CONCLUSIONS
  These findings documented for the first time that elevated plasma adiponectin suppresses the development of atherosclerosis in vivo.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishida
authors.forename: Yukio
authors.initials: Y
authors.lastname: Arita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kumada
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.forename: Naohiko
authors.initials: N
authors.lastname: Sakai
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Hideki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Terasaka
authors.forename: Toshimori
authors.initials: T
authors.lastname: Inaba
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D052242:Adiponectin; D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008264:Macrophages / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D012850:Sinus of Valsalva / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; D001057:Apolipoproteins E; D018955:CD36 Antigens; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1