Journal
ATHEROSCLEROSIS
Volume 238, Issue 2, Pages 264-270Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2014.12.017
Keywords
Proprotein convertase subtilisin kexin 9; Low-density lipoprotein; Low-density lipoprotein receptor; Protein interaction; Pleiotropic effects
Funding
- National Institutes of Health (National Heart, Lung, and Blood Institute) [R01-HL106845]
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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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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