Local adiponectin treatment reduces atherosclerotic plaque size in rabbits

In this study, we investigated the in vivo role of adiponectin, an adipocytokine, on the development of atherosclerosis in rabbits mainly using adenovirus expressing adiponectin gene (Ad-APN) and intravascular ultrasonography. Serum adiponectin concentrations in rabbits after Ad-APN local transfer to abdominal aortas increased about nine times as much as those before transfer (P<0.01), about ten times as much as the levels of endogenous adiponectin in adenovirus expressing beta-galactosidase gene (Ad-beta gal) treated rabbits (P<0.01), and about four times as much as those in the aorta of non-injured rabbits on a normal cholesterol diet (P<0.01). Ultrasonography revealed a significantly reduced atherosclerotic plaque area in abdominal aortas of rabbits infected through intima with Ad-APN, by 35.2% compared with the area before treatment (P<0.01), and by 35.8% compared with that in Ad-beta gal-treated rabbits (P<0.01). In rabbits infected through adventitia, Ad-APN treatment reduced plaque area by 28.9% as compared with the area before treatment (P<0.01) and 25.6% compared with that in Ad-beta gal-treated rabbits (P<0.01). Adiponectin significantly suppressed the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1) by 18.5% through intima transfer (P<0.05) and 26.9% through adventitia transfer (P<0.01), and intercellular adhesion molecule-1 (ICAM-1) by 40.7% through intima transfer (P<0.01), and 30.7% through adventitia transfer (P<0.01.). However, adiponectin had no effect on the expression of types I and III collagen. These results suggest that local adiponectin treatment suppresses the development of atherosclerosis in vivo in part by attenuating the expression of VCAM-1 and ICAM-1 in vascular walls.