Ultrastructural identification of monocyte-derived foam cells in fatty streak lesions.

In a previous publication (1) we demonstrated that atherosclerotic lesion development in the aorta of hypercholesterolemic pigs was preceded by intimal penetration by blood-borne mononuclear cells, and that medial smooth muscle cells were not involved in the development of fatty streak lesions in this model. The current study shows that lesions in the aortic arch do not progress beyond the fatty streak stage up to 30 wk on a hypercholesterolemic diet, and that mononuclear cell involvement continues during this period. Mononuclear cells adherent to the endothelium, or in the intima of lesion areas were identified as monocytes by the presence of peroxidase-positive granules (peroxisomes) in their cytoplasm. As well, "modified" intimal monocytes which contained a few lipid droplets and which were phagocytic, also sometimes contained peroxisomes. The results suggest that monocytes which invade the intima before or during lesion development undergo transformation into macrophage foam cells in fatty streak lesions. The absence of medial cell involvement indicates that monocytes are the major foam cell precursor in these lesions.