Proprotein convertase subtilisin/kexin type 9 potentially influences cholesterol uptake in macrophages and reverse cholesterol transport

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of low-density lipoprotein receptor (LDLRs) molecules expressed on the cell surface. Gene inactivation of PCSK9 reduces the areas of atherosclerotic lesions in mice, and the effect is mainly dependent on LDLRs. Furthermore, a positive relationship between PCSK9 and cholesterol accumulation in the wall of the aorta has been established. However, the mechanism remains unknown. As PCSK9 is mainly expressed in atherosclerotic plaque and in the liver, we hypothesize that PCSK9 might increase oxidized LDL uptake and impair macrophage-mediated reverse cholesterol transport, contributing to the development of atherosclerosis.

► PCSK9 is mainly expressed in the liver and in atherosclerotic plaques.
► PCSK9 promotes the degradation of LDLR molecules expressed on the cell surface.
► PCSK9 plays a direct role in foam cell formation and development of atherosclerosis mainly via the LDLR.
► Reverse cholesterol transport prevents the development of atherosclerosis.