Aernoud Fiolet

18 Chapter 1 Figure 1, C and D. Development of the atherosclerotic lesion. Panel C shows lesion progression that involves the migration of smooth muscle cells from the media to the intima, the proliferation of resident intimal smooth muscle cells and media-derived smooth muscle cells, and the heightened synthesis of extracellular matrix macromolecules, such as collagen, elastin, and proteoglycans. Plaque macrophages and smooth muscle cells can die in advanced lesions, some by apoptosis. Extracellular lipids derived from dead and dying cells can accumulate in the central region of plaque, often denoted the lipid or necrotic core. Advanced plaques also contain cholesterol crystals and microvessels. Panel D shows how thrombosis, the ultimate complication of atherosclerosis, often complicates the physical disruption of the atherosclerotic plaque. Panel D also shows a fracture of the plaque's fibrous cap, which has enabled blood coagulation components to come into contact with tissue factors in the plaque's interior, triggering the thrombus that extends into the vessel lumen, where it can impede blood flow. Adapted from Libby et al. 37