Understanding PCSK9 and anti-PCSK9 therapies

J Clin Lipidol. Mar-Apr 2015;9(2):170-86. doi: 10.1016/j.jacl.2015.01.001. Epub 2015 Jan 13.

Abstract

Inhibitors of proprotein convertase subtilisin kexin type 9 (PCSK9) represent a new therapeutic category of drugs for the treatment of dyslipidemia and atherosclerotic cardiovascular disease. To appreciate the efficacy of these agents and interpret research results, it is important to understand the dynamic relationship between PCSK9, low-density lipoprotein-receptors, intrahepatic cholesterol synthesis, and blood cholesterol levels. Drugs which negate the action of PCSK9 can produce substantial reductions in atherogenic lipoprotein cholesterol-carrying particles and thereby hold the potential for further reducing events associated with atherosclerotic cardiovascular disease. This article will describe and discuss PCSK9 interactive mechanisms and apply them to the interpretation of clinical trial results, which involve PCSK9 monoclonal antibodies.

Keywords: Atherosclerotic cardiovascular disease; Dyslipidemia; LDL receptors; Monoclonal antibody; Proprotein convertase subtilisin kexin type 9 (PCSK9); Statins.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / genetics
  • Atherosclerosis / pathology
  • Cholesterol / biosynthesis
  • Cholesterol / blood
  • Cholesterol / genetics
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / genetics
  • Dyslipidemias / pathology
  • Humans
  • Proprotein Convertase 9
  • Proprotein Convertases / antagonists & inhibitors
  • Proprotein Convertases / genetics*
  • Serine Endopeptidases / genetics*

Substances

  • Antibodies, Monoclonal
  • Cholesterol
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases