Atherosclerosis: Pathogenesis, Clinical Features and Treatment

Abstract

Atherosclerosis is a chronic inflammatory disease of the inner wall of large‐ and medium‐sized arteries. The condition often begins in infancy, but takes several decades to develop the full‐blown cholesterol‐rich fibrotic plaques characteristic of the mature disease and worldwide, more people die of the complications of atherosclerosis than of any other cause.

Keywords: atherogenesis; lesion; macrophages; plaque rupture; erosion

Figure 1.

Morphology of a normal artery. A healthy artery consists of three tissue layers: First, the endothelium (orange) which forms a barrier between the subendothelial tissue and the blood. It is a continuous layer covering the complete surface of all arteries. As a selective barrier, it regulates the exchange of compounds between blood and underlying tissues. Second, the media (light blue) consisting of contractile smooth muscle cells which mediate vasoconstriction and vasodilatation to maintain blood pressure. Third, the adventitia (green) which is comprised of mostly fibroblasts. It embeds the artery in the surrounding tissue. The different tissues are separated by elastic laminas termed lamina elastica interna and externa (pink).

Figure 2.

Pathogenesis of atherosclerosis. (a) Endothelial dysfunction (brown). (b) Adhesion of blood leucocytes (T lymphocytes, white; monocytes, orange) and thrombocytes (red). (c) Immigration of adhered monocytes into subendothelial areas (diapedesis). (d) Immigration of smooth muscle cells (white) from the media (light blue) into subendothelial tissues (adaptive intimal thickening) and foam cell formation (formation of an atheroma). The immigration of smooth muscle cells is accompanied by a switch to a synthetic phenotype (purple). Hence, subendothelial deposition of extracellular matrix material (purple) is increased. (e) Thickening of the lesion by enhanced foam cell formation (white spots within the cells), immigration of smooth muscle cells and further deposition of extracellular matrix proteins (purple). (f) Formation of a fibrous cap (purple) and a necrotic lipid core (white). The latter appears because of the death of foamy macrophages. (g) Due to the synthesis of proteases by macrophages, the fibrous cap covering the lipid core is thinned. (h) Plaque rupture or erosion of the endothelium occurs. (i) The contact of blood with the subendothelial tissue activates the clotting cascade and a thrombus (red) is formed. The same colours as in Figure were used to distinguish between intima, media and adventitia.

Figure 3.

Foam cell formation of macrophages. (a) Transmission electron microscopic picture of a cultured primary human monocyte‐derived macrophage. (b) Transmission electron microscopic picture of a cultured primary human macrophage‐derived foam cell. The monocyte‐derived macrophage was cultured in the presence of chemically modified LDL to induce foam cell formation. Lipid droplets appear white in the cytoplasm. The pictures were kindly prepared by Dr. Oliver Hofnagel and Prof. Dr. Horst Robenek (Leibniz Institute of Arteriosclerosis Research, Münster, Germany). (c) Fluorescence confocal laser‐scanning microscopic picture of a human THP‐1 macrophage‐derived foam cell. The cell was cultured in the presence of chemically modified LDL. Left‐hand‐side: Green staining of neutral lipids using the dye BODIPY. Centre: Red staining of adipophilin, a protein that covers and pervades lipid droplets, using specific antibodies. Right‐hand side: Merged picture of the BODIPY staining (green) and the adipophilin staining (red). These pictures are adapted from Robenek et al.. Reproduced by permission of American Society for Biochemistry & Molecular Biology.

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Further Reading

Burke B and Lewis CE (eds) (2002) The Macrophage. Oxford, Oxford University Press.

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Steinberg D (2005a) The pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part II: the early evidence linking hypercholesterolemia to coronary disease in humans. Journal of Lipid Research 46(2): 179–190.

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Lorkowski, Stefan, and Cullen, Paul(Jan 2007) Atherosclerosis: Pathogenesis, Clinical Features and Treatment. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0004228]