PCSK9: A new participant in lipophagy in regulating atherosclerosis?

Clin Chim Acta. 2019 Aug:495:358-364. doi: 10.1016/j.cca.2019.05.005. Epub 2019 May 7.

Abstract

Proprotein convertase subtilisin kexin 9 (PCSK9) regulates lipid metabolism by degrading low-density lipoprotein receptor on the surface of hepatocytes. PCSK9-mediated lipid degradation is associated with lipophagy. Lipophagy is a process by which autophagosomes selectively sequester lipid-droplet-stored lipids and are delivered to lysosomes for degradation. Lipophagy was first discovered in hepatocytes, and its occurrence provides important fundamental insights into how lipid metabolism regulates cellular physiology and pathophysiology. Furthermore, PCSK9 may regulate lipid levels by affecting lipophagy. This review will discuss recent advances by which PCSK9 mediates lipid degradation via the lipophagy pathway and present lipophagy as a potential therapeutic target for atherosclerosis.

Keywords: Atherosclerosis; Lipid metabolism; Lipophagy; Low density lipoprotein receptor; Proprotein convertase subtilisin kexin 9.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / metabolism*
  • Autophagy
  • Humans
  • Lipid Metabolism*
  • Proprotein Convertase 9 / physiology*

Substances

  • PCSK9 protein, human
  • Proprotein Convertase 9