Differentiation and Role of Macrophages in the Early Human Atherosclerotic Plaque

Abstract

New morphologic investigations on the pathogenesis of atherosclerosis have refocused attention on the role of monocytes and macrophages, especially in the early phases of the disease. The importance of macrophages in the pathogenesis of atherosclerosis had already been pointed out by Schaefer and Assmann (1980) and Schaefer (1981), and current interest in this topic is somewhat in contrast to the former concentration on smooth muscle cells. Various factors have prompted the aforementioned reorientation: Macrophages were found to be essentially involved in the intimal lipoprotein metabolism (Brown and Goldstein 1983,1986; Kelley 1991; Ylä-Herttuala et al. 1991). They incorporate cholesterol-binding lipoproteins that enter the intima, but if they have taken up more than they can possibly digest, the excess cholesterol will be stored as drop-like cytoplasmic deposits. Recent experimental data have suggested that the majority of foam cells observed in the atherosclerotic plaque must be of this origin. Foam cell transformation of smooth muscle cells was found to be rather less common (Watanabe et al. 1985; Schwartz et al. 1985). Although the functional importance of macrophages in lipoprotein metabolism has been verified in vitro, our knowledge of their behavior, especially in the human atherosclerotic plaque, is still fairly vague, as most of the morphologic studies conducted in this field have been based on experimental models (Masuda and Ross 1990a,b).