Abstract 20013: Adiponectin Protects Against Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice
Introduction & Objective: Human population-based studies have found an independent association of obesity or visceral adiposity with abdominal aortic aneurysms (AAA) presence or increasing abdominal aortic diameter. However, the molecular mechanisms that link obesity to AAA development remain largely unknown. The unbalanced production of adipokines by dysfunctional adipose tissue in obese individuals greatly contributes to the increased cardiovascular risk associated with obesity. In this study we assessed the role of adiponectin, an anti-inflammatory adipokine typically down-regulated in obese individuals, in a model of AAA using apolipoprotein E/adiponectin double-knockout (ApoE-/- Apn-/-) mice.
Methods & Results: We used an experimental model where angiotensin II (Ang II) is infused to hyperlipidemic ApoE-deficient mice for 28 days via a subcutaneous osmotic mini-pump to induce the formation of supra-renal AAA. We found that Ang II infusion for 7 days leads to a significant decrease in the expression of adiponectin in white adipose tissue in this model. Ang II infusion in male ApoE-/- Apn-/- mice led to a higher incidence of AAA and an increase in the maximal supra-renal aortic diameter compared with that of ApoE-/- mice as determined by ultrasound imaging (incidence of AAA: 100% vs. 42%, maximal aortic diameter: 2.12 ± 0.07 mm vs. 1.67 ± 0.09 mm, respectively at 28 days). Adiponectin deficiency augmented the early accumulation of macrophages into the aortic wall in Ang II-infused mice. Gene expression of the pro-inflammatory factors (TNFa, IL-1b, IL-6 and CCL2/MCP-1) was significantly increased in the supra-renal aorta of ApoE-/- Apn-/- relative to ApoE-/- mice after Ang II infusion. MMP-2 and MMP-9 activation was also augmented in the aorta of ApoE-/- Apn-/- mice compared to ApoE-/- mice.
Conclusions: These results suggest that adiponectin exerts anti-inflammatory actions in the aortic wall that may protect against Ang II-induced AAA formation and growth in hyperlipidemic ApoE-deficient mice. Since adiponectin expression is significantly decreased in obese individuals, these results provide a potential mechanistic connection between obesity and AAA development.
Author Disclosures: S. Yoshida: None. J.J. Fuster: None. K. Walsh: None.
- © 2014 by American Heart Association, Inc.