Abstract
The unstable atheroma characteristically has a thin, eccentric fibrous cap and a large
necrotic core of lipid and cellular debris. This plaque configuration is particularly
unstable because large mechanical stresses develop in the thinnest portions of the
fibrosis cap over the lipid pool. Numerous recent observations tell us that critical
biological factors other than lesion morphology also contribute to the ultimate fracture
of the fibrous cap. Matrix-degrading enzymes, particularly members of the metalloproteinase
family, are overexpressed in atherosclerotic tissue. The regions with the greatest
amounts of these enzymes are the critical high stress regions, which are usually also
infiltrated with inflammatory cells. At the cellular level a number of factors regulate
expression of these enzymes by vascular smooth muscle cells. These factors include
mechanical stimuli and cytokines known to be overexpressed in atheroma by both smooth
muscle cells and macrophages. Low density lipoprotein cholesterol in the lesion plays
a significant role in most or all of these processes, and our current understanding
of the unstable atheroma is consistent with the dramatic clinical successes of lipid-lowering
therapy.
Keywords
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Article info
Publication history
Accepted:
June 28,
1999
Identification
Copyright
© 2000 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.
