Clinical carotid atherosclerosis

Plaque formation begins with the transportation of lipoproteins into the arterial wall. Low-density lipoprotein (LDL) carries most of the cholesterol in human plasma and becomes trapped within the subendothelial space of the wall. First, the lipid component of LDL is oxidized, and this process attracts monocytes to enter the wall and become macrophages, which further the oxidative process [1]. High-density lipoprotein (HDL) has been shown to inhibit this oxidative process [2], thereby providing protection against atherogenesis. Macrophages also modify the surface protein of LDL, apoprotein B, making it unrecognizable by the LDL receptor and leading to dysregulation with resultant massive accumulation of cholesterol [1]. Smooth muscle cells begin to migrate into the lesion, stimulated by growth factors released by macrophages, platelets (which may have thrombosed beneath an area of endothelial injury), endothelial cells, and smooth muscle cells [3]. This inflammatory process results in modified LDL that is taken up by macrophages or smooth muscle cells, leading to the formation of foam cells. The accumulation of foam cells and intercellular lipid in the intimal layer constitutes the first stage of atherosclerosis called the fatty streak. Many have considered the fatty streak to be the precursor of fibrous plaque formation; however, some lesions may not develop further [4]. Virmani et al [5] classify the fatty streak as "intimal xanthomata," which refers to focal accumulations of fat-laden macrophages within the intima. We know that most intimal xanthomata will regress because the distribution of lesions in the third decade of life and beyond is very different from the fatty streaks seen in children [5]. Fibrous plaque is formed when smooth muscle cells produce a fibrous cap around the lipid core. The lipid core consists of an extracellular mass of cholesterol esters, and is lined by foam cells. The cholesterol esters accumulate as the foam cells consume more and more lipid, and eventually become necrotic and break apart, partly because of local hypoxia. The lesion grows by a continued inflammatory reaction along the shoulder regions adjacent to the edges of the lipid core. The final stage of atherosclerosis is the complicated atheroma, which is characterized by the presence of ulceration, intraplaque hemorrhage, thrombosis, and plates of calcification. Studies of coronary arteries have shown calcium granules begin deposition immediately with the formation of the lipid core, although plates and lumps of calcium form in more advanced lesions [4]. The complicated atheroma is frequently associated with a clinically acute event.