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 ␤-galactosidase (Ad-␤gal). The plasma adiponectin levels in Ad-APN-treated mice increased 48 times as much as those in Ad-␤gal 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-␤gal-treated mice (PϽ0.05). In the lesions of Ad-APN-treated mice, the lipid droplets became smaller compared with Ad-␤gal-treated mice (PϽ0.01). 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-␣ 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.

Mechanisms by which diabetes increases cardiovascular disease

“…It reduces TNF-α-mediated adhesion of THP-1 monocytes to and induction of ICAM-1 in human coronary artery endothelial cells (HCAEC) [49]. In Apoe −/− mice, treatment with a recombinant adenovirus expressing human adiponectin resulted in increased adiponectin serum levels and decrease of atherosclerotic lesion size by about 30 % [50]. mRNA for VCAM-1 and scavenger receptor class A were significantly reduced in lesions from these mice [50].…”

“…In Apoe −/− mice, treatment with a recombinant adenovirus expressing human adiponectin resulted in increased adiponectin serum levels and decrease of atherosclerotic lesion size by about 30 % [50]. mRNA for VCAM-1 and scavenger receptor class A were significantly reduced in lesions from these mice [50]. Interestingly, PPARγ agonists are known to promote adipocyte differentiation and also to increase adiponectin transcription and serum levels [51].…”

Effect of anti-oxidants, Ricetrienol and α-tocopherol, on adipocytokine abnormalities and fatty liver in Otsuka Long-Evans Tokushima Fatty diabetic rats

“…Several studies have reported the reduction of plasma adiponectin in patients with macrovascular disease 19,20 . It has also been reported that overexpression of plasma adiponectin in apo‐E KO mice improves atherosclerosis 21 . Resistin also has been reported to be involved in the development of atherosclerosis 22 .…”

Adiponectin produced in coronary circulation regulates coronary flow reserve in nondiabetic patients with angiographically normal coronary arteries

“…2 Systemic clinical hypoadiponectinemia is closely associated with obesity, type 2 diabetes, and coronary artery disease (CAD). 4 Furuhashi et al recently reported that transcardiac adiponectin levels are significantly decreased in nondiabetic patients with CAD, but not in diabetic patients with the same condition.…”