The Monocyte and Endothelial Injury in Atherogenesis

Abstract

The macrophage foam cell has been recognized as a hallmark of the atherosclerotic plaque for over a century. However, the potential importance of the blood monocyte in atherosclerosis was first pointed out by Leary as late as 1941. Poole and Florey (1958) later discussed the blood as a source of lesion foam cells in hypercholesterolemic rabbits, and demonstrated a macrophage traversing the endothelium. Still and O’Neal (1962) were the first to demonstrate, ultrastructurally, the adherence to and penetration of the endothelium by monocytes in hypercholesterolemic animals, a finding subsequently described by numerous others under a wide variety of conditions (Jerome and Lewis 1984, 1985; Joris et al. 1983; Gerrity 1981a, 1981b). However, until the last decade, only Kim et al. (1966) attempted to establish the circulating monocyte/macrophage as a major factor in atherogenesis, and it was unclear whether lipid accumulation in lesion macrophage foam cells occurred due to sequestration of blood lipophages in the arterial wall, or by the accumulation of intimal lipid by monocytes which had previously traversed the endothelium. Furthermore, the “response to injury” hypothesis in its initial format (Ross and Glomset 1976) did not define any potential role of the blood monocyte in lesion initiation, and the relationships, if any, between endothelial injury and monocyte penetration of the intima remained unclear.