Weight loss in obese C57BL/6 mice limits adventitial expansion of established angiotensin II-induced abdominal aortic aneurysms

Police SB, Putnam K, Thatcher S, Batifoulier-Yiannikouris F, Daugherty A, Cassis LA. Weight loss in obese C57BL/6 mice limits adventitial expansion of established angiotensin II-induced abdominal aortic aneurysms. Am J Physiol Heart Circ Physiol 298: H1932-H1938, 2010. First published March 19, 2010; doi:10.1152/ajpheart.00961.2009.-Previous studies demonstrated that obesity increases inflammation in periaortic adipose tissue and promotes angiotensin II (ANG II)-induced abdominal aortic aneurysms (AAAs). We sought to determine whether weight loss of obese C57BL/6 mice would influence the progression of established AAAs. Male C57BL/6 mice were fed a high-fat diet (HF) for 4 mo and then infused with either saline or ANG II (1,000 ng.kg(-1).min(-1)) for 3 mo. Mice with dilated suprarenal aortas at 28 days of ANG II infusion were designated to groups fed the HF (HF/HF) or a low-fat diet (LF; 10% kcal as fat; HF/LF) to induce weight loss for the last 2 mo of infusions. Suprarenal aortic lumen diameters of obese mice were increased by ANG II infusion at day 28 (day 0: 1.03 +/- 0.02; day 28: 1.86 +/- 0.14 mm; P < 0.05), but did not progress with continued infusion in HF/HF mice. Moreover, aortic lumen diameters were not different between groups (HF/HF: 1.89 +/- 0.15; HF/LF: 1.79 +/- 0.18 mm). However, maximal diameters of excised AAAs were decreased with weight loss (HF/HF: 2.00 +/- 0.11; HF/LF: 1.55 +/- 0.13 mm; P < 0.05) and had reduced adventitial areas (HF/HF: 1.18 +/- 0.10; HF/LF: 0.54 +/- 0.02 mm2; P < 0.05). Neovascularization of aortic adventitias was strikingly decreased in HF/LF mice (HF/HF: 43 +/- 5; HF/LF: 12 +/- 2 endothelial cells/adventitial area; P < 0.05). ANG II-induced elevations in adipose mRNA abundance of CD105, an adipose-derived stem cell marker, were abolished with weight loss. These results demonstrate that weight loss limits adventitial expansion of ANG II-induced AAAs. Reduced neovascularization from weight loss may limit progression of AAAs.