Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis.
Obesity is more linked to vascular disease, including atherosclerosis and restenotic change, after balloon angioplasty. The precise mechanism linking obesity and vascular disease is still unclear. Previously we have demonstrated that the plasma levels of adiponectin, an adipose-derived hormone, decreases in obese subjects, and that hypoadiponectinemia is associated to ischemic heart disease. In current the study, we investigated the in vivo role of adiponectin on the neointimal thickening after artery injury using adiponectin-deficient mice and adiponectin-producing adenovirus. Adiponectin-deficient mice showed severe neointimal thickening and increased proliferation of vascular smooth muscle cells in mechanically injured arteries. Adenovirus-mediated supplement of adiponectin attenuated neointimal proliferation. In cultured smooth muscle cells, adiponectin attenuated DNA synthesis induced by growth factors including platelet-derived growth factor, heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), basic fibroblast growth factor, and EGF and cell proliferation and migration induced by HB-EGF. In cultured endothelial cells, adiponectin attenuated HB-EGF expression stimulated by tumor necrosis factor alpha. The current study suggests an adipo-vascular axis, a direct link between fat and artery. A therapeutic strategy to increase plasma adiponectin should be useful in preventing vascular restenosis after angioplasty.
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Morihiro
M
Matsuda
Iichiro
I
Shimomura
Masataka
M
Sata
Yukio
Y
Arita
Makoto
M
Nishida
Norikazu
N
Maeda
Masahiro
M
Kumada
Yoshihisa
Y
Okamoto
Hiroyuki
H
Nagaretani
Hitoshi
H
Nishizawa
Ken
K
Kishida
Ryutaro
R
Komuro
Noriyuki
N
Ouchi
Shinji
S
Kihara
Ryozo
R
Nagai
Tohru
T
Funahashi
Yuji
Y
Matsuzawa
D000256:Adenoviridae; D052242:Adiponectin; D000818:Animals; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D003094:Collagen / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D003327:Coronary Disease / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D004261:DNA Replication; D004730:Endothelium, Vascular / Q000473:pathology* / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology*; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D017539:Tunica Intima / Q000473:pathology*; D014652:Vascular Diseases / Q000209:etiology / Q000235:genetics*
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D003094:Collagen