Phospholipid hydrolytic enzymes in a 'cesspool' of arterial intimal lipoproteins: a mechanism for atherogenic lipid accumulation.

Most of the lipid in atherosclerotic fibrous plaques is extracellular. How does it get there? Hakala and coworkers1 describe in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology a pathway involving enzymatic hydrolysis of phospholipids in LDL, leading to lipoprotein aggregation and fusion and hence, to accumulation of lipid droplets. The process is enabled and enhanced in the presence of arterial proteoglycans. This extracellular pathway should be distinguished from the commonly postulated cellular pathway involving uptake of modified LDL in macrophage foam cells, which subsequently die and leave the accumulated lipid in an extracellular location.