Obesity promotes the formation and weight loss limits the progression of angiotensin II-induced abdominal aortic aneurysms

The purpose of this research was to determine whether the physiological and biological changes which occur with obesity promote AngII-induced AAA formation and progression.;We investigated whether obesity promotes AngII-induced AAA formation by utilizing diet-induced and genetic models of obesity. By feeding mice a HF diet; we demonstrated that AAA incidence increased progressively as a function of the duration of HF feeding and the degree of abdominal obesity in C57BL/6 mice. In additional studies, we demonstrated that obesity due to leptin deficiency enhanced AngII-induced AAA formation. Regardless of the model of obesity, increased AAA formation was associated with increased abdominal adiposity, increased plasma concentrations of resistin, and macrophage infiltration into abdominal adipose tissue in dose proximity to AAA. Collectively these studies established that obesity increases AAA formation associated with macrophage infiltration into abdominal adipose tissue, suggesting a contribution of localized and systemic inflammation as mechanisms underlying enhanced AAA susceptibility with obesity.;Weight loss has been demonstrated to reverse or reduce deleterious effects of obesity; thus, we investigated whether weight loss influenced AAA progression. Diet-induced obese mice were infused with AngII for 4 weeks, at which time mice identified with AAAs were either maintained on a HF diet or switched to a LF diet to promote weight loss. Mice switched to a LF diet exhibited dramatic weight loss in the form of reduced abdominal adiposity.;Weight loss was associated with decreased adventitial neovascularization surrounding a formed AAA, as assessed by ex-vivo external diameter and pathological analyses of adventitial area. Interestingly, weight loss was not associated with reduced macrophage content of abdominal adipose tissue. These results suggest that weight loss reduced angiogenesis, likely limiting adventitial expansion.;In these studies, obesity and weight loss differentially influence AAA progression. Results of early studies suggested that obesity-induced inflammation was underlying increased AAA formation; however, results from the weight loss study suggested that decreased angiogenic activity---but not adipose-derived inflammation---was associated with reduced adventitial neovascularization of formed AAA. Regardless of the mechanisms involved, results of this research advocate a role for obesity in the formation and progression of AngII-induced AAA.;KEYWORDS: Obesity, Angiotensin II, Abdominal aortic aneurysm, Weight loss, Inflammation.