Abstract
Proprotein convertase subtilisin kexin type 9 (PCSK9) is a circulatory ligand that terminates the lifecycle of the low-density lipoprotein (LDL) receptor (LDLR) thus affecting plasma LDL-cholesterol (LDL-C) levels. Recent evidence shows that in addition to the straightforward mechanism of action, there are more complex interactions between PCSK9, LDLR and plasma lipoprotein levels, including: (a) the presence of both parallel and reciprocal regulation of surface LDLR and plasma PCSK9; (b) a correlation between PCSK9 and LDL-C levels dependent not only on the fact that PCSK9 removes hepatic LDLR, but also due to the fact that up to 40% of plasma PCSK9 is physically associated with LDL; and (c) an association between plasma PCSK9 production and the assembly and secretion of triglyceride-rich lipoproteins. The effect of PCSK9 on LDLR is being successfully utilized toward the development of anti-PCSK9 therapies to reduce plasma LDL-C levels. Current biochemical research has uncovered additional mechanisms of action and interacting partners for PCSK9, and this opens the way for a more thorough understanding of the regulation, metabolism, and effects of this interesting protein.
Original language | English (US) |
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Pages (from-to) | 264-270 |
Number of pages | 7 |
Journal | Atherosclerosis |
Volume | 238 |
Issue number | 2 |
DOIs | |
State | Published - Feb 1 2015 |
Externally published | Yes |
Keywords
- Low-density lipoprotein
- Low-density lipoprotein receptor
- Pleiotropic effects
- Proprotein convertase subtilisin kexin 9
- Protein interaction
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine