Aernoud Fiolet

17 General introduction and thesis outline Figure 1, A and B. Development of the atherosclerotic lesion. The normal muscular artery and the cell changes that occur during disease progression to thrombosis are shown. Panel A shows the normal artery that contains three layers. The inner layer, the tunica intima, is lined with a monolayer of endothelial cells that is in contact with the blood over the basement membrane. In contrast to many animal species used for atherosclerosis experiments, the human intima contains resident smooth muscle cells. The middle layer, or tunica media, contains smooth muscle cells embedded in a complex extracellular matrix. Arteries affected by obstructive atherosclerosis generally have the structure of muscular arteries. The arteries often studied in experimental atherosclerosis are elastic arteries, which have clearly demarcated laminae in the tunica media, where layers of elastin lie between the strata of smooth muscle cells. The adventitia, the outer layer of arteries, contains mast cells, nerve endings, and microvessels. Panel B shows the initial steps of atherosclerosis that include the adhesion of blood leukocytes to the activated endothelial monolayer, directed migration of the bound leukocytes into the intima, maturation of monocytes (the most numerous of the leukocytes recruited) into macrophages, and their uptake of lipids, yielding foam cells. Adapted from Libby et al. 37