Figure 1. The response-to-retention model for the pathogenesis of atherosclerosis. Arrows are colour coded to indicate crucial mechanisms in retention and modification. The key initiating step in atherogenesis is the retention and aggregation of cholesterol-rich atherogenic apolipoprotein B lipoproteins within the arterial wall (yellow). Then, maladaptive local responses to the retained and modified lipoproteins lead to plaque growth and progression (red). Processes to the left of the vertical dashed line are characteristic of early atherosclerotic plaques and hence remain entirely or nearly entirely reversible, while processes to the right of the vertical dashed line are characteristic of advanced, end-stage plaques and hence appear to be only partially reversible. Foam cell pertains to a macrophage or smooth muscle cell that has accumulated intracellular droplets of lipid. C-TRL, cholesterol and triglyceride-rich lipoprotein; IDL, intermediate-density lipoprotein; IEL, internal elastic lamina; IFN, interferon; IL, interleukin; LDL, low-density lipoprotein; LP, lipoprotein; Lp(a), lipoprotein(a); LpL, lipoprotein lipase; MMPs, matrix metalloproteinases; PGs, proteoglycans; SMase, the secretory acid sphingomyelinase; SMC, smooth muscle cell; TF, tissue factor; UC, unesterified cholesterol. Reproduced with permission from Williams,¹⁸ which was adapted from Williams and Tabas.¹⁶.