On the function and homeostasis of PCSK9: Reciprocal interaction with LDLR and additional lipid effects

Hagai Tavori, Shirya Rashid, Sergio Fazio

    Research output: Contribution to journalArticle

    42 Citations (Scopus)

    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 languageEnglish (US)
    Pages (from-to)264-270
    Number of pages7
    JournalAtherosclerosis
    Volume238
    Issue number2
    DOIs
    StatePublished - Feb 1 2015

    Fingerprint

    LDL Receptors
    Homeostasis
    Lipids
    LDL Lipoproteins
    Proprotein Convertase 9
    LDL Cholesterol
    Lipoproteins
    Triglycerides
    Ligands

    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

    Cite this

    On the function and homeostasis of PCSK9 : Reciprocal interaction with LDLR and additional lipid effects. / Tavori, Hagai; Rashid, Shirya; Fazio, Sergio.

    In: Atherosclerosis, Vol. 238, No. 2, 01.02.2015, p. 264-270.

    Research output: Contribution to journalArticle

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