Trivedi et al β-Arrestin-2 and Abdominal Aortic Aneurysms 1221 Histology and Immunohistochemistry

Abdominal aortic aneurysms (AAAs) are a common vascular condition associated with several risk factors, including advanced age, male sex, smoking, and hypercholesterolemia. AAA formation begins as an abnormal dilation of the aorta, which may gradually expand over a period of years followed by eventual weakening and rupture of the vessel wall, resulting in mortality in ≈90% of cases. The pathophysiology of AAAs can be roughly categorized into 2 processes: inflammation and extracellular matrix degeneration. Inflammation is exemplified by the release of inflammatory mediators such as monocyte chemoattractant protein-1 (MCP-1) and interleukin 6 and the resultant infiltration of inflammatory cells, particularly macrophages, into the vessel wall. Inflammatory cells are a major source of proteolytic enzymes such as matrix metalloproteinase (MMP) 2 and MMP9, which are known to disrupt the structural integrity of the vessel wall and to degrade the components of the extracellular matrix such as elastin and collagen. This extracellular matrix degeneration and vascular remodeling contribute to the progression and severity of the disease. Currently, there are no pharmacological treatments for AAAs, with endovascular or surgical repair being the only options. A widely used mouse model of AAAs involves chronic infusion of angiotensin II (AngII), and this model displays multiple characteristics of human AAAs and has provided mechanistic insight into the formation and progression of the disease. AngII mediates many of its physiological and pathological effects by activating the G-protein–coupled Molecular Medicine