Atherothrombosis and High-Risk Plaque
Part I: Evolving Concepts
Valentin Fuster, MD, PhD, FACC*,
Pedro R. Moreno, MD, FACC*,*,
Zahi A. Fayad, PhD, FACC*,
Roberto Corti, MD, FACC and
Juan J. Badimon, PhD, FACC*
* Zena and Michael A. Wiener Cardiovascular Institute and the Marie-Josee and Henry R. Kravis Cardiovascular Health Center, The Mount Sinai School of Medicine, New York, New York
Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
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Figure 1 Cross-sectioned coronary artery containing a ruptured plaque with a non-occlusive platelet-rich thrombus superimposed. The actual defect in the fibrous cap is not seen in this section but is located nearby, documented by the presence of extravasated radiographic contrast medium (postmortem coronary angiography) in the soft, lipid-rich core just beneath the thin, inflamed fibrous cap. Trichrome stain, rendering thrombus red, collagen blue, and lipid colorless. Adapted with permission from Falk E and Fuster V. Atherogenesis and its determinants. In: Hursts the Heart. 10th edition. Fuster V, et al., editors. McGraw-Hill, 2001:1065–94.
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Figure 2 Histologic example of a high-risk, vulnerable plaque. (a) Large lipid-rich core with a thin fibrous cap. The lumen contains contrast medium injected postmortem. (b) Higher magnification showing macrophages (>25 per high-power field) beneath a very thin cap (<65 µm in thickness). Extravasated erythrocytes with plaque hemorrhage within the core indicate plaque rupture nearby. Trichrome stain, rendering lipid colorless, collagen blue, and erythrocytes red. Adapted with permission from Schaar JA, et al. Eur Heart J 2004;25:1077–82.
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Figure 3 Plaque erosion. Cross section of a coronary artery containing a stenotic atherosclerotic plaque with an occlusive thrombosis superimposed. The endothelium is missing at the plaque-thrombus interface, but the plaque surface is otherwise intact. Trichrome stain, rendering thrombus red, collagen blue, and lipid colorless. Courtesy of Dr. Erling Falk, Aarhus, Denmark.
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Figure 4 Clinicopathologic correlation of asymptomatic atherosclerosis leading to symptomatic atherothrombosis. Modified from Corti R, Fuster V. J Thromb Thrombolysis 2004;17:35–44.
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Figure 5 Simplified scheme representing seven categories of lesions. Dashed lines reflect controversy regarding etiology. The processes leading to lesion progression are listed between categories. Reproduced with permission from Virmani R, et al. Arterioscler Thromb Vasc Biol 2000;20:1262.
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Figure 6 Healthy endothelium under laminar flow conditions and no risk factors. A single molecule, nitric oxide (NO), is involved in multifactorial pathways preventing monocyte adhesion, platelet aggregation, and smooth muscle cell proliferation. PGI2 = prostacyclin 2; SMC = smooth muscle cell; tPA = tissue plasminogen activator.
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Figure 7 Diseased endothelium with non-laminar flow, low-density lipoprotein (LDL) deposition, cell adhesion molecule (CAM) expression, macrophage migration, tissue factor (TF), and matrix metalloproteinase (MMP) expression leading to smooth muscle cell (SMC) proliferation and vasa vasorum neovascularization. PDGF = platelet-derived growth factor; PAI-1 = plasminogen activator inhibitor-1; TXA2 = thromboxane A2.
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Figure 8 Examples of human atherosclerotic calcification. (A) Microcalcifications identified by light microscopy within the lipid core of a transitional (type IV) coronary plaque (black arrows). (B) Coarse calcification seen in an advanced (type Vb) coronary plaque. Reproduced with permission from Stary HC. A Slide Atlas of Atherosclerosis Progression and Regression. New York, NY: Parthenon Publisher Group Inc., 1999.
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Figure 9 Coronary neovessels from adventitial vasa vasorum nurture the vessel wall through the first order (parallel) and the second order (perpendicular). Reproduced with permission from Kwon HM, et al. J Clin Invest 1998;101:1551–6.
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Figure 10 (A) High-power image of microvessels identified with the monoclonal endothelial cell marker CD34 linked to a blue chromogen. (B) High-power image from the plaque shoulder region showing CD34-positive microvessels in blue contrasting sharply with CD68/CD3-positive inflammatory cells linked to a red chromogen. (C) Microvessels at the tunica media (purple chromogen) contrasting with smooth muscle cells linked to a brown chromogen using alpha-actin marker. (D) Corresponding high power from C, showing disarray of smooth muscle cells in brown and microvessels in purple. Reproduced with permission from Moreno PR, et al. Circulation 2004;110:2032–8.
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Figure 11 Microvessels as a pathway for macrophage entry/exit to atherosclerotic plaques. High-power image showing CD34-positive microvessels (blue) and intraluminal, monocyte-derived macrophages (red) circulating within the plaque, as highlighted by the red arrows. Courtesy of Dr. Purushothaman, Mount Sinai Hospital, 2005.
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Figure 12 Plaque vulnerability, disruption, and thrombosis: anatomical changes leading to acute coronary syndrome and subsequent plaque remodeling. An element of vasoconstriction is usually present. Modified with permission from Theroux and Fuster (136).
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Figure 13 Atherothrombosis: a variable mix of chronic atherosclerosis and acute thrombosis. Cross-sectioned arterial bifurcation illustrating a collagen-rich (blue-stained) plaque in the circumflex branch (left) and a lipid-rich and ruptured plaque with a non-occlusive thrombosis superimposed in the obtuse branch (right). C = contrast in the lumen; Ca = calcification; T = thrombosis. Adapted from Falk E, Prediman S, Fuster V. Coronary plaque disruption. Circulation 1995;92:657–71.
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Figure 14 Interactions between platelet activation, tissue factor (TF) vesicle expression from plaque macrophages, and activation of the coagulation cascade. Ca2+ = calcium; vWF = von Willebrand factor.
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