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Stabilization of atherosclerotic plaques: an update

Seppo Ylä-Herttuala, Jacob Fog Bentzon, Mat Daemen, Erling Falk, Hector M. Garcia-Garcia, Joerg Herrmann, Imo Hoefer, Suvi Jauhiainen, J. Wouter Jukema, Rob Krams, Brenda R. Kwak, Nikolaus Marx, Marek Naruszewicz, Andrew Newby, Gerard Pasterkamp, Patrick W.J.C. Serruys, Johannes Waltenberger, Christian Weber, Lale Tokgözoglu,
DOI: http://dx.doi.org/10.1093/eurheartj/eht301 3251-3258 First published online: 21 August 2013

Vulnerable plaques

The majority of coronary thrombi (∼75%) is caused by plaque rupture.1,2 Prototype of the rupture-prone plaque contains a large, soft, lipid-rich necrotic core with a thin and inflamed fibrous cap, so-called thin-cap fibroatheroma (TCFA) (Figure 1).3,4 Other common features include expansive remodelling, large plaque size, plaque haemorrhage, neovascularization, adventitial inflammation, and ‘spotty’ calcifications.4 Thin-cap fibroatheroma caps are usually <65 µm thick.4 Figure 2 summarizes factors contributing to the formation of vulnerable plaques. No distinct morphological features have been identified for the erosion-prone plaques, but they are usually rarely associated with expansive remodelling, scarcely calcified, and contain only limited inflammation.2,5

Figure 1

Cross-sectioned coronary artery showing a ruptured thin-cap fibroatheroma. The fibrous cap is very thin near the rupture site (between arrows) and a non-obstructive mural thrombus (asterisks) is bordering the gap in the disrupted cap. A haemorrhage has penetrated from the lumen through the gap into the lipid-rich necrotic core in which the characteristic cholesterol clefts are clearly seen. The lumen contains contrast medium injected postmortem. Overview in inset. Trichrome, staining collagen blue, and thrombus and haemorrhage red.

Figure 2

Factors contributing to the formation of vulnerable plaques. MCP-1, monocyte chemotactic protein-1; MIF, migration inhibitory factor; TNFα, tumour necrosis factor-α; ILs, interleukins; MMPs, matrix metalloproteinases; TIMPs, tissue inhibitors of metalloproteinases; PDGFs, platelet-derived growth factors; VEGFs, vascular endothelial growth factors; FGFs, fibroblast growth factors; Mφ, macrophages.

Inflammatory cells, cytokines, chemokines, and growth factors

Vulnerable plaques contain monocytes, macrophages, and T-cells. Of the T-cells, CD4+ T-helper (Th) cells are the most prominent.6 T-cells can differentiate into a Th1 phenotype, which secretes and responds to IFN-γ or a Th2 phenotype, which secretes and responds to IL-4, IL-10, and IL-13 (Figure 3). T-cells promote the vulnerability of plaques through their effects on macrophages. Similarly, there are two main plaque macrophage phenotypes: …