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. METHODS AND 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.

journal_name

Circulation

journal_title

Circulation

authors

Okamoto Y,Kihara S,Ouchi N,Nishida M,Arita Y,Kumada M,Ohashi K,Sakai N,Shimomura I,Kobayashi H,Terasaka N,Inaba T,Funahashi T,Matsuzawa Y

doi

10.1161/01.cir.0000042707.50032.19

subject

Has Abstract

pub_date

2002-11-26 00:00:00

pages

2767-70

issue

22

eissn

0009-7322

issn

1524-4539

journal_volume

106

pub_type

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