The role of PCSK9 in coronary vascular disease development

Abstract

Proprotein convertase subtilisin/keksin type 9 (PCSK9) is a promising target to lower serum cholesterol. PCSK9 binds to the receptor of low-density lipoprotein (LDL-R), and complex PCSK9/LDL-R leads to degradation in endosomes and lysosomes and LDL concentration has increased in blood. Gain-of-function mutations in the gene encoding PCSK9 induse high-plasma LDL levels and increase of cardiovascular risk. Loss-of-function mutations in the gene encoding PCSK9 induse low-plasma LDL levels and decrease of cardiovascular risk without known unwanted effects on individual health. Clinical studies have demonstrated that inhibition of PCSK9 alone and in addition to statins therapy highly reduces LDL concentrations in serum. This review presents the current data on the regulation of PCSK9, its molecular function in lipid homeostasis and new fact on the extra-hepatic effects PCSK9.