Abstract 10354: Adiponectin Adenovirus Restores Endothelial Function by Decreasing Inflammation and Oxidative Stress in Type 2 Diabetic Mice
Adiponectin (APN) is a 30-kDa protein exclusively secreted by adipose tissue. APN is deficient in the serum and in aorta protein expression in type 2 diabetic mice (P<0.05), which suggests APN may play an important role in vascular dysfunction and the development of type 2 diabetes. Accordingly, we hypothesized that administering APN will restore endothelial function in aortas in type 2 diabetic mice. To test this hypothesis, we injected adiponectin adeno-virus (Ad-APN) or β-galactosidase (control virus, Ad-βgal) via tail-vein in control (m Leprdb) and diabetic mice (Leprdb) and studied vascular function of aorta ex vivo. Serum level of APN is increased 3–4 folds in both m Leprdb and Leprdb after Ad-APN injection. Endothelium-dependent vasodilator acetylcholine (Ach)-induced vasodilation was blunted in Leprdb compare to m Leprdb, but sodium nitroprusside (SNP)-induced endothelium-independent vasodilation was identical. Ad-APN improved endothelial function in Leprdb compare to Ad-βgal whereas Ad-APN had no effect on m Leprdb. Immunoblot results showed that interferon gamma (IFN-γ), pro-inflammatory cytokine was markedly increased in aorta of Leprdb, Ad-APN treatment decreased IFN-γ suggesting APN may suppress inflammation process. In addition, proteins expression of both gp91phox, one of NAD(P)H oxidase subunits and nitrotyrosine, oxidative stress marker, were markedly increased in Leprdb, but Ad-APN treatment decreased protein expressions of gp91phox and nitrotyrosine in the aorta. This suggests that APN contributes to an increase in nitric oxide bioavailability by decreasing superoxide production in the aorta. However, superoxide dismutase (SOD) 1,2 and 3 protein expressions were comparable among groups. APN appears to play an important role in the remediation of vascular dysfunction in the aorta by preventing inflammation and excessive oxidative stress in type 2 diabetes.
- © 2010 by American Heart Association, Inc.