Medline ® Abstracts for References 5,17

To examine the hypothesis that a tendency toward aneurysmal degeneration of the abdominal aorta may be inherited, we compared the family histories of 250 patients with abdominal aortic aneurysm (AAA) with those of 250 control subjects. Among the control subjects, six (2.4%) reported having a first-degree relative with an aneurysm, compared with 48 (19.2%) of the patients with AAA. After adjustment for age and sex, this corresponds to an estimated 11.6-fold increase in AAA risk among persons with an affected first-degree relative. This study suggests that the relatives of patients with AAA may themselves be at significantly increased risk for the development of aneurysmal degeneration. Because early diagnosis and elective management of AAA significantly prolong life, noninvasive screening to detect early AAA formation may be warranted in relatives of patients with AAA.

The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves breakdown of the elastic laminae. Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage, but whether endogenous local inhibitors counterbalance these proteases is unknown. We show here that, whereas cystatin C is normally expressed in vascular wall smooth muscle cells (SMCs), this cysteine protease inhibitor is severely reduced in both atherosclerotic and aneurysmal aortic lesions. Furthermore, increased abdominal aortic diameter among 122 patients screened by ultrasonography correlated inversely with serum cystatin C levels. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins, whose elastolytic activity could be blocked when cystatin C secretion was induced by treatment with TGF-beta(1). The findings highlight a potentially important role for imbalance between cysteine proteases and cystatin C in arterial wall remodeling and establish that cystatin C deficiency occurs in vascular disease.