FIGURE 2.

Localization of macrophage subtypes in human atherosclerotic lesions. Atherosclerosis is initiated with a local inflammatory response and the presence of monocyte-derived macrophages. In the intima, macrophages (mainly M1 phenotype) scavenge lipoprotein particles and become foam cells. The secreta of foam cells and M1 macrophages promote lipoprotein retention and sustain inflammation, leading to a further M1 macrophage polarization during atherosclerosis progression. The cholesterol crystals deposited in the plaque can further promote M1 polarization. However, fibrous caps contain similar amounts of M1 and M2 macrophage. In advanced lesions, the gradual accumulation of apoptotic debris results in formation of a necrotic core, which triggers further inflammation and necrosis. Of note, M1 macrophages are predominantly found in the plaque shoulder and lipid core, whereas M2 macrophages localized in the adventitia and areas of neovascularization or outside the lipid core. The degradation of the extracellular matrix and cycles accumulation of lipids may induce plaque rupture and the following thrombosis. In vulnerable plaques, the number of M1 macrophages is increased, while the number of M2 type macrophages is decreased. It is worth noted that M2 macrophages can phagocytose apoptotic M1 macrophages, contributing to the resolution of inflammation. In regressing plaques, there are more M2 macrophages than M1 type macrophages.