Adiponectin Reduces Atherosclerosis in Apolipoprotein E-Deficient Mice

TLDR

Dysregulation of adipocyte‑derived bioactive molecules contributes to atherosclerosis development. The study examined whether elevated plasma adiponectin reduces atherosclerosis in ApoE‑deficient mice using adenoviral delivery. Recombinant adenovirus expressing human adiponectin was used to raise plasma levels, and immunohistochemistry revealed its migration to foam cells in fatty streak lesions. Ad‑APN treatment increased plasma adiponectin 48‑fold, reduced aortic sinus lesion area by 30%, decreased lipid droplet size, and downregulated VCAM‑1 and class A scavenger receptor expression, demonstrating that elevated plasma adiponectin suppresses atherosclerosis in vivo.

Abstract

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.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.These findings documented for the first time that elevated plasma adiponectin suppresses the development of atherosclerosis in vivo.