LAUSR

Aortic disease arises from abnormalities in size or structure of the vessel wall. An (fusiform) aneurysm is a localized dilatation of the aorta, usually defined as >150% of the normal diameter for a given segment. Aortic dissection is bleeding into the media layer, often with propagation of a false lumen. Both diseases can occur independently, although dilated aortas are at increased risk of dissection, dissected aortas have increased expansion rates, and either process can result in vessel rupture. Aneurysms and dissections are broadly classified as affecting the thoracic (supradiaphragmatic) or abdominal (infradiaphragmatic) aorta. Thoracic aortic disease is characterized by medial degeneration, whereas pathology of the abdominal aorta includes substantial inflammatory infiltrates, marked loss of smooth muscle cells (SMCs), and frequent luminal thrombus. Additionally, thoracic but not abdominal aneurysm and dissection is associated with numerous genetic mutations, including genes coding for fibrillin-1 causing Marfan syndrome or components of the transforming growth factor-β (TGFβ)–signaling pathway causing Loeys–Dietz syndrome, such as TGFβ receptors, TGFβ ligands, and SMAD transcription factors. See accompanying article on page 2102 Mouse models have recapitulated many pathological aspects of aortic aneurysm and dissection and are informative in testing mechanisms of disease and potential therapeutics. A popular model is the infusion of angiotensin II (AngII) to hypercholesterolemic mice, first described by the Daugherty group. Dissection of the suprarenal abdominal aorta occurs within 4 to 10 days in the majority of animals and aneurysms restricted to this region progressively develop from vascular remodeling for several weeks.1 Normocholesterolemic mice infused with AngII have less abdominal but similar thoracic aortic disease manifesting as infrequent dissection and rupture with modest dilatation of the ascending aorta by 7 days.2,3 Although a convenient experimental model, there is limited evidence for AngII hyperactivity in clinical disease. Hence, AngII inhibitors are not prescribed for …