Genetic investigation into the aetiology of abdominal aortic aneurysms

[Truncated abstract] An abdominal aortic aneurysm (AAA) is a permanent and irreversible localised dilation of the aortic wall. AAA is characterised by the degeneration of normal arterial wall architecture, proteolytic fragmentation of the medial elastin, loss of smooth muscle cells (SMCs) and remodelling of the extracellular matrix (ECM). The major complication associated with AAAs is their inability to resist the dilating force of arterial pressure which increases the chance of rupture, leading to massive internal haemorrhage and often death. One of the striking hallmarks of AAAs is the extensive degeneration of the tunica media. The principal risk factors associated with AAAs appear to be increased age, male gender, smoking and a family history of AAA. Proteolytic enzymes play a major role in the pathogenesis of AAAs, particularly the serine proteases, cysteine proteases and matrix metalloproteinases (MMPs) that are able to degrade fibrillar collagens (types I, III, V). Increased levels of both cysteine protease and the MMPs have been detected in AAA tissue, with the latter emerging as the principal class of proteolytic enzyme and showing a direct correlation with aneurysm size (Longo et al., 2002)...