A Real Player in Atherogenesis

An important early step in atherosclerosis is binding of apolipoprotein B-100 (apoB-100)– containing lipoproteins (VLDL, IDL, and LDL) to the proteoglycan component of the extracellular matrix of the arterial intima.1,2 When oxidative agents or enzymes attack the proteoglycan-bound lipoproteins, they become oxidatively modified, and when various intimal proteases or lipases hydrolyze them, they become nonoxidatively modified. Whereas oxidation of proteoglycan-bound apoB-100–containing particles triggers their release and subsequent uptake by macrophages, the nonoxidative modifications do the opposite: they enhance the strength of particle binding to proteoglycans.3 In addition, such nonoxidatively modified apoB-100–containing lipoprotein particles tend to aggregate and fuse, which allows progressive extracellular accumulation of lipoprotein lipids, a key phenomenon in atherogenesis. The nonoxidative modifications can also lead to intracellular lipid accumulation and so induce foam cell formation, a hallmark of early atherogenesis.4 Thus, local modification of apoB-100–containing lipoproteins leads to both extraand intracellular accumulation of lipids in the arterial intima.