Abstract 3614: Adiponectin Inhibits Vascular Inflammation and Rapid Progression of Atherosclerosis Induced by Angiotensin II

Adiponectin, an adipocytokine derived from adipose tissue, has anti-inflammatory and antiatherogenic properties and low plasma adiponectin levels are associated with the metabolic syndrome and cardiovascular disease. However, it is unknown whether elevated plasma adiponectin levels provide atheroprotection against angiotensin II (AngII)-induced vascular inflammation and accelerated atherosclerosis. We investigated whether adenoviral adiponectin expression provides protection against AngII-induced inflammation and atherosclerosis. Thirteen week-old low-density lipoprotein receptor-deficient (LDLR −/− ) mice were fed Western diet and infused with Ang-II. Mice were injected with 5 X 10 8 particles of adenovirus expressing either GFP (Ad-GFP, n=16/group) or mouse adiponectin (Ad-APN, n=16/group). Eight weeks after injection, plasma adiponectin levels in Ad-APN-injected mice were increased 12-fold compared to control Ad-GFP mice (306.4 mg/dL vs 25.3 mg/dL). Elevation of plasma adiponectin levels led to a significant increase in plasma HDL levels (23.6% increase vs. control), whereas the plasma cholesterol and triglyceride levels were unchanged. Quantification of atherosclerosis in the entire aortas by en face method, revealed a significant inhibition of atherosclerosis in Ad-APN mice (45% reduction, p<0.01 vs. Ad-GFP mice). Furthermore, adiponectin expression substantially inhibited the mRNA expression of inflammatory and atherogenic genes (ICAM-1, osteopontin, MCP-1 and CCR2) in the vessel wall. Interestingly, adiponectin also increased the mRNA expression of critical reverse cholesterol transport genes, ABCA1 and ABCG1, in the aorta. These results demonstrate that increasing plasma adiponectin levels may be an effective therapeutic strategy to inhibit angiotensin-II induced vascular inflammation and rapid progression of atherosclerosis.