individuals often rupture, even when small. In Marfan syndrome (Chapter 7), defective synthesis of the scaffolding protein fibrillin leads to increased bioavailability of TGF-β in the aortic wall, with subsequent dilation due to dysregulated signaling and progressive loss of elastic tissue. Defective type III collagen synthesis leading to aneurysm formation is a hallmark of type IV Ehlers-Danlos syndrome (Chapter 7).
Excessive connective tissue degradation. Increased matrix metalloprotease expression by macrophages in atherosclerotic plaque can contribute to aneurysm development by degrading arterial ECM in the arterial wall; similarly, decreased tissue inhibitors of metalloprotease expression can also tip the balance toward net ECM degradation. A genetic predisposition to aneurysm formation in the setting of inflammation may be related to polymorphisms in these factors.
Loss of SMCs or change in the SMC synthetic phenotype. Atherosclerotic thickening of the intima can cause ischemia of the inner media by increasing the diffusion distance from the lumen. Conversely, systemic hypertension can cause luminal narrowing of the aortic vasa vasorum, leading to ischemia of the outer media. Such ischemia results in SMC loss as well as aortic “degenerative changes,” which include fibrosis (replacing distensible elastic tissue), inadequate ECM synthesis, and accumulation of increasing amounts of amorphous proteoglycans. Histologically, these changes are collectively called cystic medial degeneration (
Fig. 10.18 ), although no true cysts are formed. Such changes are nonspecific; they can occur whenever ECM synthesis is defective, including in inherited disorders such as Marfan syndrome and acquired conditions such as scurvy.
The two most important predisposing conditions for aortic aneurysms are atherosclerosis and hypertension.
Atherosclerosis is the dominant factor in abdominal aortic aneurysms, while hypertension is associated with ascending aortic aneurysms. Other conditions that weaken vessel walls and lead to aneurysms include trauma, vasculitis (see later), congenital defects, and infections, giving rise to so-called “mycotic aneurysms.” Mycotic aneurysms may result from (1) embolization of a septic embolus, usually as a complication of infective endocarditis; (2) extension of an adjacent suppurative process; or (3) direct infection of an arterial wall by circulating organisms. Tertiary syphilis is a rare cause of aortic aneurysms. A predilection of the spirochetes for the vasa vasorum of the ascending thoracic aorta—and the subsequent immune response to them—results in an obliterative endarteritis that compromises blood flow to the media; the ensuing ischemic injury leads to aneurysmal dilation that occasionally also can involve the aortic valve annulus.
Aneurysms occurring as a consequence of atherosclerosis form most commonly in the abdominal aorta and common iliac arteries, and may also involve the aortic arch and descending thoracic aorta. Abdominal aortic aneurysms (AAAs) occur more frequently in men and in smokers and rarely develop before 50 years of age. Atherosclerosis is a major cause of AAA, but other factors clearly contribute, since the incidence is less than 5% in men older than 60 years of age despite the almost universal presence of abdominal aortic atherosclerosis in this population.