Abstract 243: Adiponectin Inhibits Angiotensin II-induced Abdominal Aortic Aneurysm Formation

Abstract

BACKGROUND Abdominal aortic aneurysms (AAA) are characterized by inflammation, loss of smooth muscle cells (SMC) and degradation of extracellular matrix in the vessel wall. Adiponectin, an adipokine produced by adipose tissue, exerts profound anti-inflammatory and anti-atherogenic effects on vascular cells. However, the role of adiponectin on AAA has not been studied. We investigated the impact of increased plasma adiponectin levels on angiotensin II (AngII)-induced AAA formation in mice. METHOD AND RESULTS Male low-density lipoprotein receptor-deficient (LDLR -/- ) mice fed on a high-fat diet were infused with AngII (25 mg/kg/min) for 8 weeks to induce AAA. Mice infused with saline was used as controls. A recombinant adenoviral vector encoding mouse adiponectin (Ad-APN) was injected intravenously to induce adiponectin expression. A recombinant adenovirus expressing green fluorescence protein (GFP) was used as a control (Ad-GFP). Eight weeks after injection, plasma adiponectin levels were 10-fold higher (253.9±59.0 μg/mL) in Ad-APN mice compared to Ad-GFP mice (25.2±3.8 μg/mL, P<0.001). Aortic diameter was significantly reduced in Ad-APN mice compared to Ad-GFP mice (60% reduction). This was accompanied by decreased frequency and size of abdominal atherosclerotic lesions in Ad-APN mice compared to Ad-GFP mice. Histologically, elastin was degraded in all AngII-infused mice compared to saline-infused mice. However elastin was more preserved in Ad-APN mice compared to Ad-GFP mice (P<0.05). Gene expression analysis of the abdominal aorta revealed a decrease of CD3e (P<0.05) but no profound changes in inflammatory genes, IL-6, TNF-α and CD68. Decreased mRNA expression of the SMC marker SM22α was observed in all AngII-infused mice compared to saline-infused mice. Expression of SM22α was two-fold higher in the abdominal aorta in Ad-APN mice than in Ad-GFP mice (P<0.05). CONCLUSION These results provide first evidence that adiponectin overexpression significantly inhibits AngII-induced AAA formation in LDLR -/- mice. The protective actions of adiponectin appear to be mediated, in part, through preservation of SMC content and elastin in the vascular wall. The mechanisms of adiponectin inhibiting AAA formation deserve further attention.