THE ROLE OF THE MONOCYTE IN ATHEROGENESIS .1. TRANSITION OF BLOOD-BORNE MONOCYTES INTO FOAM CELLS IN FATTY LESIONS

Abstract

Aortic arch lesions do not progress beyond the fatty cell lesion stage for up to 30 wk of a moderate cholesterol/lard diet, although they become more extensive in area in Yorkshire pigs. Mononuclear cells were found adherent to the endothelium, in endothelial junctions and in the intima during this period, and were ultrastructurally identified as monocytes by the presence of peroxidase-positive granules (peroxisomes) in their cytoplasm. Lesion areas with nonspecific esterase activity correlated well with Sudan IV staining. Intimal monocytes and altered intimal monocytes with an enlarged cytoplasm and containing a few lipid droplets were phagocytic by their uptake of ferritin, which had penetrated the intima after i.v. injection. Circulating monocytes and those adherent to the endothelial surface did not contain ferritin in these animals. Blood mononuclear cells associated with lesion formation in this model are apparently monocytes, which subsequently 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.