What is the role of inflammation in plaque destabilization?

Updated: Dec 30, 2019
  • Author: Elena R Ladich, MD; Chief Editor: Allen Patrick Burke, MD  more...
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Pathologic studies have demonstrated that inflammation contributes to the acute thrombotic complications of atherosclerosis. For example, it has been shown that fibrous cap thickness is related to the extent of macrophage infiltrate. Thin fibrous caps tend to demonstrate a greater number of macrophages compared with thick fibrous caps. Macrophages produce matrix metalloproteinases (MMPs), zinc-dependent endopeptidases, that possess catalytic activity.

Much interest has been focused on the role of MMPs as the main cause of fibrous cap disruption in plaque rupture. [15] Fibrillar collagens, especially type I, provide most of the tensile strength to the fibrous cap. The initial proteolytic nick in the collagen chain is provided by MMPs-1, -8 and -13, whereas the gelatinases MMP-2 and MMP-9 support collagen breakdown. It has been shown that atheromatous rather than fibrous plaques preferentially exhibit type I collagen cleavage occurring at sites that are rich in macrophages expressing both MMP-1 and MMP-13.

Clinical studies of coronary artery disease have shown that increased circulating levels of C-reactive protein (CRP), a positive acute-phase reactant, are an independent risk factor for cardiovascular disease. Pathologic studies have shown that the median serum CRP is significantly higher in victims of sudden coronary death dying from plaque rupture, erosion, and stable plaque relative to control subjects dying of noncoronary conditions.

In addition, there has been considerable interest in the role of other inflammatory proteins such as pregnancy-associated plasma protein-A, interleukin (IL)-6, IL-12, and oxidative products that may reflect the presence of chronic inflammation in the arterial wall or elsewhere in the body and thus may increase the risk of atherosclerosis.

A study by van Dijk et al found that transient CXCL13 expression, restricted presence of B cells in human atherosclerosis, along with formation of nonfunctional extranodal lymphoid structures in the phase preceding plaque rupture. The authors hypothesize that this indicates a change in the “inflammatory footprint” before and during plaque destabilization. [16]

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