Scavenging new insights into atherogenesis

According to current hypotheses, atherosclerosis begins to develop when lipoproteins accumulate in the arterial intima and become chemically modified, thus initiating local vessel wall inflammation and attracting monocytes from the circulation. Modified lipoproteins are taken up avidly by monocyte-derived macrophages, and the resulting fat-laden macrophages (now known as foam cells) reside in the vessel wall and exacerbate the local inflammatory response. Since LDL receptor–deficient (LDLR-deficient) macrophages are not attenuated in their ability to develop into foam cells, it has long been known that foam cell formation requires receptors distinct from the LDLR. Moreover, macrophages do not readily take up native plasma lipoproteins in large amounts and will only become foam cells when exposed to oxidized, acetylated, or otherwise covalently modified lipoproteins. Hence, the discovery of the “scavenger” receptors for modified lipoproteins and the elucidation of lipid-modification processes are of crucial importance in our understanding of atherogenesis.