Medline ® Abstracts for References 11,32

Formation of the atherosclerotic intima must involve altered metabolism of the elastin-rich arterial extracellular matrix. Proteases potentially involved in these processes remain unclear. This study examined the expression of the potent elastases cathepsins S and K in human atheroma. Normal arteries contained little or no cathepsin K or S. In contrast, macrophages in atheroma contained abundant immunoreactive cathepsins K and S. Intimal smooth muscle cells (SMC), especially cells appearing to traverse the internal elastic laminae, also contained these enzymes. Extracts of atheromatous tissues had approximately twofold greater elastase-specific activity than extracts of uninvolved arteries, mostly due to cysteine proteases. Cultured human SMC displayed no immunoreactive cathepsins K and S and exhibited little or no elastolytic activity when incubated with insoluble elastin. SMC stimulated with the atheroma-associated cytokines IL-1beta or IFN-gamma secreted active cathepsin S and degraded substantial insoluble elastin (15-20 microg/10(6) cells/24 h). A selective inhibitor of cathepsin S blocked>80% of this elastolytic activity. The presence of cathepsins K and S at sites of vascular matrix remodeling and the ability of SMC and macrophages to use these enzymes to degrade elastin supports a role for elastolytic cathepsins in vessel wall remodeling and identifies novel therapeutic targets in regulating plaque stability.

BACKGROUND: This retrospective analysis of prospectively collected abdominal aortic aneurysm (AAA) screening data aimed to identify predictors of AAA-related events (surgery or death) with a view to better targeting of screening.

METHODS: For the interval 1984-2007, data for 1649 subjects with an AAA were collected prospectively as part of the Chichester AAA screening programme. This included serial aortic size measurements, blood pressure, risk factors for arterial disease and concurrent medications. AAA growth rates were adjusted for risk factor confounders using flexible hierarchical modelling. AAA growth distribution was analysed using Silverman's test of multimodality.

RESULTS: Some 1231 subjects met the inclusion criteria of having more than one scan and a surveillance interval of over 3 months. AAA growth showed a bimodal pattern with nearly 50 per cent of all aneurysms never progressing to surgery or rupture. Adjusted annual AAA growth rates of at least 2 mm significantly predicted AAA-related events.

CONCLUSION: This analysis identified a bimodal growth pattern for AAA, with a significant association between annual AAA growth rate of at least 2 mm and AAA-related events.