p53 and Atherosclerosis

Subendothelial macrophages are a major cellularcomponent of atherosclerotic lesions. In response tosubendothelial retention of modified lipoproteins,1,2 blood-borne monocytes enter the subendothelial space, differentiate into macrophages, and accumulate large amounts of lipoprotein-derived cholesterol (foam cells).3,4 Specific consequences of macrophage foam-cell formation include both physical effects, such as intimal thickening, and biological effects, such as internalization of lipopro-teins and secretion of biologically active molecules.3,5 Importantly, atherosclerosis is significantly attenuated in mice with deficient lesional macrophages attributable to dysfunctional macrophage colony–stimulating factor or decreased monocyte chemotaxis.6 – 8 Remarkably, subpopulations of lesional macrophages show signs of proliferation,9 and other subpopulations are noted to have morphological characteristics as well as biochemical