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 β-galactosidase (Ad-βgal). The plasma adiponectin levels in Ad-APN–treated mice increased 48 times as much as those in Ad-βgal 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-βgal–treated mice (P<0.05). In the lesions of Ad-APN–treated mice, the lipid droplets became smaller compared with Ad-βgal–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-α 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.