Atherosclerosis and macrophages.

Atherosclerosis is undoubtedly a disease of many facets and in this review we have merely touched one angle of this issue. The best-established cause of the disease is hypercholesterolemia. Since the important role of macrophages in lipoprotein metabolism has been confirmed, current interest is focused on the role of macrophages in atherosclerosis. The origin and tissue distribution of foam cells have been discussed in detail, because they are the principal cells in the earliest lesions, the so-called fatty streaks. Once thought to be derived exclusively from smooth muscle cells, foam cells are now known to originate largely from monocytes that enter the intima and become transformed into macrophages. Exactly how monocytes are recruited and retained in the artery wall is not fully understood, but it is certain that the initial event involves adhesion to the endothelial surface followed by penetration under the influence of a chemotactic factor(s). Hypercholesterolemia contributes much to this phenomenon by affecting both monocyte-macrophages and endothelial cells. Intensive current research is increasing our understanding of the dynamic interaction between macrophages and both lipoproteins and vascular cells, and its immediate relevance to lesion formation. Closer scrutiny of the biology and molecular mechanism of the process of atherosclerosis may ultimately permit intervention in and slowing of the progress of this catastrophic human disease using new modalities.