Prime mover in atherosclerosis

Elevated blood levels of lipoproteins containing apolipoprotein (apo) B are implicated in the development of atherosclerosis in humans, but the triggering event has remained unclear. In June 13 Nature, Kristina Skålén and colleagues from Göteborg University, Sweden, show that the retention of apoB-containing low-density lipoproteins (LDL) by proteoglycans immediately beneath the endothelial layer is a central event in early atherogenesis (Nature 2002, 417:750-754).

Skålén et al. used mice expressing proteoglycan-binding-defective LDL. They observed that when fed a diet that promotes atherogenesis, these mice develop plaques more slowly than control mice expressing the normal human apoB100 protein. The LDL particles from transgenic mice carrying normal and mutated human apoB100 were transported similarly across the endothelial lining of the wall and showed the same susceptibility to oxidation, inflammatory properties and capture by macrophages.

"Given these new findings, measurements of the ability of LDL to bind to proteoglycans might produce a helpful diagnostic ...