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• W2131327563 abstract "Although not all forms of aneurysm, which may vary in location, are of atherosclerotic origin, atheroma is probably the main cause of acquired abdominal aneurysms in humans. In 1992, Reed et al1 described the similarity of risk factors for occlusive and aneurysmal diseases in a cohort of 8000 men and concluded that atheroma was a causal pathway to aneurysm development. This common initial pathway has been recently confirmed through a postmortem morphological approach in humans.2 The usual occlusive forms of atheroma involve intimal accumulation of material including lipids, matrix proteins, and cells, whereas the medial layer remains largely uninjured, consisting of smooth muscle cells (SMCs) and insoluble extracellular matrix. In contrast, aneurysm development involves proteolytic injury to the medial layer, including the degradation of elastin and collagen, SMC rarefaction, and compensatory fibrosis of the adventitia. Therefore, the question raised is this: What are the biological determinants that preferentially switch the outcome of atheroma from intimal accumulation of biological materials to medial destruction? The involvement of protease and antiprotease systems in the evolution of atheroma is now well documented both in aneurysm formation3 and in plaque rupture (see Libby4 for a review). These systems involve matrix metalloproteinases (MMPs), which are able to degrade the insoluble extracellular matrix, their activation and inhibition by tissue inhibitors (TIMPs),5 and the plasminogen activators and their inhibitors (PAIs).6See p 1440 In the current issue of Arteriosclerosis, Thrombosis, and Vascular Biology , Silence and coworkers7 have explored this interesting question of the switch from intimal accumulation to medial destruction in atheroma and implicate MMP-3 activity in this phenomenon with an experimental genetic approach in mice by cross-breeding ApoE−/− mice and mice deficient for the MMP-3 gene. The authors show that disruption of the MMP-3 gene in hypercholesterolemic atherosclerotic …" @default.
• W2131327563 created "2016-06-24" @default.
• W2131327563 creator A5030152912 @default.
• W2131327563 date "2001-09-01" @default.
• W2131327563 modified "2023-10-18" @default.
• W2131327563 title "Contrasting Outcomes of Atheroma Evolution" @default.
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• W2131327563 doi "https://doi.org/10.1161/atvb.21.9.1389" @default.
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