Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9)

Basic Res Cardiol. 2015 Mar;110(2):4. doi: 10.1007/s00395-015-0463-z. Epub 2015 Jan 20.

Abstract

The proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising treatment target to lower serum cholesterol, a major risk factor of cardiovascular diseases. Gain-of-function mutations of PCSK9 are associated with hypercholesterolemia and increased risk of cardiovascular events. Conversely, loss-of-function mutations cause low-plasma LDL-C levels and a reduction of cardiovascular risk without known unwanted effects on individual health. Experimental studies have revealed that PCSK9 reduces the hepatic uptake of LDL-C by increasing the endosomal and lysosomal degradation of LDL receptors (LDLR). A number of clinical studies have demonstrated that inhibition of PCSK9 alone and in addition to statins potently reduces serum LDL-C concentrations. This review summarizes the current data on the regulation of PCSK9, its molecular function in lipid homeostasis and the emerging evidence on the extra-hepatic effects of PCSK9.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / physiopathology*
  • Homeostasis
  • Humans
  • Proprotein Convertase 9
  • Proprotein Convertases / physiology*
  • Serine Endopeptidases / physiology*

Substances

  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases