Abdominal aortic aneurysms occur in up to 9% of adults older than 65 years of age, and the rupture of these aneurysms accounts for about 15,000 deaths in the United States annually. 1 Approximately 33,000 patients undergo repair of abdominal aortic aneurysms each year, with associated illness, death, and health care costs. Smoking is a major risk factor. Although aggressive management of hypertension and hyperlipidemia is recommended in patients with abdominal aortic aneurysms, therapies for these conditions have little effect on aneurysm growth and rupture. In this context, a recent study by Satoh and colleagues2 is welcome because it sheds new light on how abdominal aortic aneurysms form and thereby rekindles interest in a therapy that was shown to protect against experimental aneurysm formation more than a decade ago.

Epidemiologic and pathological studies have yielded few clues to the cause of abdominal aortic aneurysms. Although abdominal aortic aneurysms frequently occur in patients with atherosclerosis and the two disease processes share several common risk factors, atherosclerotic lesions are predominantly intimal in location, whereas the media and adventitia are primarily involved in aneurysms. The hallmark pathologic feature of atherosclerosis is foam-cell formation, whereas aneurysms are typified by intense oxidative stress, inflammation, matrix degradation, and apoptosis of smooth-muscle cells. 3 Inhibitors of matrix metalloproteinase are currently being tested in human aneurysmal disease, but their efficacy may be limited, in part because they are directed toward only one aspect of the disease process; thus, targeting factors that contribute to multiple aspects of the pathologic process of aneurysms would probably be of greater benefit. Studies in animal models have shown that angiotensin II induces vascular oxidative stress, inflammation, matrix degradation, and apoptosis of smooth-muscle cells and contributes experimentally to aneurysm formation. 4 Studies in humans also suggest a role for angiotensin II in the pathogenesis of the disease. However, the cellular mechanisms that link these pathologic processes together to produce abdominal aortic aneurysms remain to be elucidated.