Figure 2

Macrophages in atherosclerotic plaque development. A-C representative heterogeneous foam cells from carotid atherosclerotic plaques. A: CD86 (brown), B: CD163 (brown) ADRP (green), C: CD206 (brown). D and E: macrophage collagen I expression. D: CD163 (green), procollagen I (red), nuclei (blue), CD163 and procollagen I co-expression (yellow). Inset: closer magnification of the cell in D indicated by white arrow head. E: CD86 (green: examples indicated by white arrow heads), procollagen I (red), nuclei (blue). Note, no CD86/procollagen I co-expression is evident as seen by absence of yellow. F: Proposed role of macrophage involvement in plaque progression. Lipoprotein enters the vessel wall where it is retained, in part, by binding to proteoglycans. Monocytes are recruited into the atherosclerotic plaque where they differentiate into different macrophage phenotypes (predominantly M2 in the early plaque) and uptake modified lipid adopting heterogenous foam cell forms (see also A-C). Apoptosis of the macrophages, in particular M2, is accompanied by efferocytosis, also primarily by M2 macrophages. As the plaque adopts an increasingly inflammatory environment, M1 foam cells predominate and defective efferocytosis increases, with subsequent necrosis leading to the formation of the necrotic core. In the advanced plaque, intraplaque haemorrhage promotes the formation of Mhem macrophages, which are athero-protective, partly due to reduced lipid accumulation and the production of collagen I. In contrast, M1 macrophages accumulate in the shoulder of the plaque contributing to thinning of the cap through MMP production. The destabilisation of the plaque leads to rupture of the plaque and thrombus formation. IPH = intraplaque haemorrhage, MV = microvessels, Mϕ = macrophage, PG = proteoglycan.