Atherosclerosis: Pathogenesis, Clinical Features and Treatment


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.



Ast M and Frishman WH (1990) Bile acid sequestrants. Journal of Clinical Pharmacology 30(2): 99–106.

Cullen P, Rauterberg J and Lorkowski S (2005) The pathogenesis of arteriosclerosis.Handbook of Experimental Pharmacology 170: 3–70.

Kohlman‐Trigoboff D (2004) Hypertension management in patients with vascular disease. Journal of Vascular Nursing 22(2): 53–56.

Lees RS, Cashin‐Hemphill L and Lees AM (1999) Non‐pharmacological lowering of low‐density lipoprotein by apheresis and surgical techniques. Current Opinion in Lipidology 10(6): 575–579.

Paoletti R, Bolego C and Cignarella A (2005) Lipid and non‐lipid effects of statins. Handbook of Experimental Pharmacology 170: 365–388.

Patel SB (2004) Ezetimibe: a novel cholesterol‐lowering agent that highlights novel physiologic pathways. Current Cardiology Reports 6(6): 439–442.

Phillips DR, Conley PB, Sinha U and Andre P (2005) Therapeutic approaches in arterial thrombosis. Journal of Thrombosis and Haemostasis 3(8): 1577–1589.

Robenek H, Lorkowski S, Schnoor M and Troyer D (2005) Spatial integration of TIP47 and adipophilin in macrophage lipid bodies. The Journal of Biological Chemistry 280(7): 5789–5794.

Robillard R, Fontaine C, Chinetti G et al. (2005) Fibrates. Handbook of Experimental Pharmacology 170: 389–406.

Van der Steeg WA, El‐Harchaoui K, Kuivenhoven JA and Kastelein JJ (2005) Ester transfer protein inhibition: a next step in the fight against cardiovascular disease? Current Drug Targets – Cardiovascular & Hematological Disorders 5(6): 481–488.

Von Eckardstein A (2005) Risk factors for atherosclerotic vascular disease. Handbook of Experimental Pharmacology 170: 71–105.

Further Reading

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

Choudhury RP, Lee JM and Greaves DR (2005) Mechanisms of disease: macrophage‐derived foam cells emerging as therapeutic targets in atherosclerosis. Nature Clinical Practice Cardiovascular Medicine 2(6): 309–315.

Glass CK and Witztum JL (2001) Atherosclerosis. The road ahead. Cell 104(4): 503–516.

Goldschmidt‐Clermont PJ, Creager MA, Losordo DW et al. (2005) Atherosclerosis 2005: recent discoveries and novel hypotheses. Circulation 112(21): 3348–3353.

Libby P (2002) Inflammation in atherosclerosis. Nature 420(6917): 868–874.

Lusis AJ (2000) Atherosclerosis. Nature 407(6801): 233–241.

Maxfield FR and Tabas I (2005) Role of cholesterol and lipid organization in disease. Nature 438(7068): 612–621.

Steinberg D (2004) The pathogenesis of atherosclerosis An interpretive history of the cholesterol controversy: part I. Journal of Lipid Research 45(9): 1583–1593.

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.

Steinberg D (2005b) The pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part III: mechanistically defining the role of hyperlipidemia. Journal of Lipid Research 46(10): 2037–2051.

Steinberg D (2006a) The pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part IV: the 1984 coronary primary prevention trial ends it – almost. Journal of Lipid Research 47(1): 1–14.

Steinberg D (2006b) The pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part V: the discovery of the statins and the end of the controversy. Journal of Lipid Research 47(7): 1339–1351.

Von Eckardstein A (ed.) (2005) Arteriosclerosis: influence of diet and drugs. Handbook of Experimental Pharmacology.Heidelberg, Springer.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

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