Association of PCSK9 with human plasma Lipoproteins

Abstract

Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is a serine protease primarily expressed in the liver. The main function of circulating PCSK9 relates to its binding to the low-density lipoprotein receptor (LDL-R) in hepatocytes, increasing its endosomal and lysosomal degradation. This results in the inhibition of LDL-R recycling to the cell surface and therefore in the reduction of the hepatic LDL uptake, leading to the increase in plasma levels of LDL-cholesterol. Several studies have demonstrated that the plasma levels of PCSK9 are correlated with those of the ApoB-containing lipoproteins; LDL, Lp(a) and Triglyceride-Rich Lipoproteins (TRL). Furthermore, it has been shown that PCSK9 binds to the LDL and Lp(a) particles and significantly influences TRL metabolism. By contrast, controversial results exist concerning the association of PCSK9 with High Density Lipoprotein (HDL). In the present review we present existing data on the association of PCSK9 with human plasma lipoprotein particles and its possible pathophysiological role.