Stages in the development of atherosclerotic plaques. a, In the first stages, lipoprotein is trapped in the subendothelial matrix. The freeze-etch electron micrograph shows the accumulation of 23-nm LDL particles (circled) in the matrix of a rabbit atrial-ventricular valve following incubation with LDL (inset). An endothelial cell at lower left shows the plasma membrane (MEMB) and cytoplasma (CYTO)71. Magnification ×141,372; scale bar, 0.1 μm. b, Lipoprotein aggregation is seen in this freeze-etch electron micrograph of rabbit intima following administration of a bolus of LDL. The aggregated particles are surrounded by matrix and collagen fibrils (asterisk)72. Magnification ×52,876; scale bar, 0.2 μm. c, Monocyte transmigration. The thin-section electron micrograph of a cross-section of the aorta of a 9-week-old apoE-deficient mouse shows a monocyte (arrow) moving between two endothelial cells (arrowheads) to enter the intima (int). The asterisk denotes a cluster of lipid underneath the endothelial cell1. Magnification ×10,078; scale bar, 0.5 μm. d, Foam-cell formation. Freeze-etch electron micrograph of the cytoplasm of a macrophage foam cell in the intima of a rabbit fed a high-fat diet for two weeks. Large lipid droplets with the onion skin configuration typical of cholesterol esters (ce) as well as other lipid-filled compartments (arrows) can be recognized. Some compartments contain large aggregated LDL particles (asterisk) resembling those in b. Magnification ×21,542; scale bar, 0.5 μm. e, Fibrous lesion. Light micrograph (×400) of a section of an advanced human coronary atherosclerotic lesion that has been immunostained for the macrophage-specific antigen EMB-11 (red). A, adventitia; I, intima; IEL, internal elastic lamina; M, media. Photographs courtesy of A. Mottino, J. Frank and T. Drake, UCLA.