Beyond LDL: What Role for PCSK9 in Triglyceride-Rich Lipoprotein Metabolism?

Abstract

Elevated plasma triglyceride (TG) levels are an independent risk factor for cardiovascular disease (CVD). Proprotein convertase subtilisin-kexin 9 (PCSK9) - a protein therapeutically targeted to lower plasma cholesterol levels - might regulate plasma TG-rich lipoprotein (TRL) levels. We provide a timely and critical review of the current evidence for a role of PCSK9 in TRL metabolism by assessing the impact of PCSK9 gene variants, by reviewing recent clinical data with PCSK9 inhibitors, and by describing the potential mechanisms by which PCSK9 might regulate TRL metabolism. We conclude that the impact of PCSK9 on TRL metabolism is relatively modest, especially compared to its impact on cholesterol metabolism.

Keywords: apolipoprotein B; genetic variants; low-density lipoprotein receptor; proprotein convertase subtilisin-kexin 9; triglyceride-rich lipoproteins.