Obesity Promotes Inflammation in Periaortic Adipose Tissue and Angiotensin II-Induced Abdominal Aortic Aneurysm Formation

Abstract

Objective— Obesity promotes macrophage infiltration into adipose tissue and is associated with increases in several cardiovascular diseases. Infusion of angiotensin II (AngII) to mice induces formation of abdominal aortic aneurysms (AAAs) with profound medial and adventitial macrophage infiltration. We sought to determine whether obesity promotes macrophage infiltration and proinflammatory cytokines in periaortic adipose tissue surrounding abdominal aortas and increases AngII-induced AAAs. Methods and Results— Hypertrophied white adipocytes surrounded abdominal aortas, whereas brown adipocytes surrounded thoracic aortas of obese mice. mRNA abundance of macrophage proinflammatory chemokines and their receptors were elevated with obesity to a greater extent in abdominal compared to thoracic periaortic adipose tissue. Periaortic adipose tissue explants surrounding abdominal aortas of obese mice released greater concentrations of MCP-1 and promoted more macrophage migration than explants from thoracic aortas. Male C57BL/6 mice were fed a high-fat (HF) diet for 1, 2, or 4 months and then infused with AngII (1000 ng/kg/min) for 28 days. AAA incidence increased progressively with the duration of HF feeding (18%, 36%,and 60%, respectively). Similarly, AngII-infused ob/ob mice exhibited increased AAAs compared to lean controls (76% compared to 32%, respectively, P <0.05). Infusion of AngII to obese mice promoted further macrophage infiltration into periaortic and visceral adipose tissue, and obese mice exhibiting AAAs had greater macrophage content in visceral adipose tissue than mice not developing AAAs. Conclusions— Increased macrophage accumulation in periaortic adipose tissue surrounding abdominal aortas of AngII-infused obese mice is associated with enhanced AAA formation.

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

“…Although we found similarities in mitral and aortic valve leaflet thickening, mitral valve remodeling was not within the scope of the current study. Cytokines and matrix metalloproteinases associated with LepA effects on the vessel wall were not examined in these models, and we did not explore leptin‐independent mechanisms of ascending aortic aneurysm formation that function through macrophage recruitment and signaling 51. These factors warrant a dedicated study.…”

Visceral adiposity is not associated with abdominal aortic aneurysm presence and growth

“…We postulated that visceral adiposity could be an important contributor to the pathogenesis of AAA based on findings in an animal study. 17 Aortic inflammation is believed to play a critical role in AAA pathogenesis. [33][34][35] The majority of arteries, including the abdominal aorta, are surrounded by peri-vascular adipose tissue.…”

“…36 It has been postulated that visceral adipose tissue may promote periaortic inflammation. 12,17 White adipose tissue in particular has been implicated in the secretion of pro-inflammatory chemokines. 36 The localised nature of adipose secretions from visceral deposits suggests that peri-vascular adipose tissue is able to secrete chemokines in high concentrations which could promote aortic inflammation.…”

Mouse models of the metabolic syndrome

“…diet versus monogenic), and the method of measuring hypertension. For example, in C57BL/6J mice that are fed the same high-fat diet, diet-induced obesity can have differential effects on systolic blood pressure when measured by radiotelemetry and the tail cuff method (Gupte et al, 2008;Police et al, 2009;Symons et al, 2009). It is possible that the magnitude of the blood pressure increases (10-15 mmHg systolic pressure) in studies using radiotelemetry in obese mice may not be within the range of sensitivity of tail cuff methods.…”