Proprotein convertase subtilisin kexin type 9 promotes intestinal overproduction of triglyceride-rich apolipoprotein B lipoproteins through both low-density lipoprotein receptor-dependent and -independent mechanisms

Shirya Rashid, Hagai Tavori, Patrick E. Brown, Macrae F. Linton, Jane He, Ilaria Giunzioni, Sergio Fazio

    Research output: Contribution to journalArticle

    81 Citations (Scopus)

    Abstract

    Background - Proprotein convertase subtilisin kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein (LDL) receptor (LDLR), and its deficiency in humans results in low plasma LDL cholesterol and protection against coronary heart disease. Recent evidence indicates that PCSK9 also modulates the metabolism of triglyceride-rich apolipoprotein B (apoB) lipoproteins, another important coronary heart disease risk factor. Here, we studied the effects of physiological levels of PCSK9 on intestinal triglyceride-rich apoB lipoprotein production and elucidated for the first time the cellular and molecular mechanisms involved. Methods and Results - Treatment of human enterocytes (CaCo-2 cells) with recombinant human PCSK9 (10 μg/mL for 24 hours) increased cellular and secreted apoB48 and apoB100 by 40% to 55% each (P

    Original languageEnglish (US)
    Pages (from-to)431-441
    Number of pages11
    JournalCirculation
    Volume130
    Issue number5
    DOIs
    StatePublished - Jul 29 2014

    Fingerprint

    LDL Receptors
    Apolipoproteins B
    Lipoproteins
    Triglycerides
    Coronary Disease
    Apolipoprotein B-48
    Caco-2 Cells
    Enterocytes
    LDL Cholesterol
    Proprotein Convertase 9

    Keywords

    • Apolipoproteins
    • Lipids
    • Molecular biology
    • Pathophysiology
    • Receptors, lipoprotein
    • Risk factors

    ASJC Scopus subject areas

    • Physiology (medical)
    • Cardiology and Cardiovascular Medicine

    Cite this

    Proprotein convertase subtilisin kexin type 9 promotes intestinal overproduction of triglyceride-rich apolipoprotein B lipoproteins through both low-density lipoprotein receptor-dependent and -independent mechanisms. / Rashid, Shirya; Tavori, Hagai; Brown, Patrick E.; Linton, Macrae F.; He, Jane; Giunzioni, Ilaria; Fazio, Sergio.

    In: Circulation, Vol. 130, No. 5, 29.07.2014, p. 431-441.

    Research output: Contribution to journalArticle

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    abstract = "Background - Proprotein convertase subtilisin kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein (LDL) receptor (LDLR), and its deficiency in humans results in low plasma LDL cholesterol and protection against coronary heart disease. Recent evidence indicates that PCSK9 also modulates the metabolism of triglyceride-rich apolipoprotein B (apoB) lipoproteins, another important coronary heart disease risk factor. Here, we studied the effects of physiological levels of PCSK9 on intestinal triglyceride-rich apoB lipoprotein production and elucidated for the first time the cellular and molecular mechanisms involved. Methods and Results - Treatment of human enterocytes (CaCo-2 cells) with recombinant human PCSK9 (10 μg/mL for 24 hours) increased cellular and secreted apoB48 and apoB100 by 40{\%} to 55{\%} each (P",
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    AU - Rashid, Shirya

    AU - Tavori, Hagai

    AU - Brown, Patrick E.

    AU - Linton, Macrae F.

    AU - He, Jane

    AU - Giunzioni, Ilaria

    AU - Fazio, Sergio

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    AB - Background - Proprotein convertase subtilisin kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein (LDL) receptor (LDLR), and its deficiency in humans results in low plasma LDL cholesterol and protection against coronary heart disease. Recent evidence indicates that PCSK9 also modulates the metabolism of triglyceride-rich apolipoprotein B (apoB) lipoproteins, another important coronary heart disease risk factor. Here, we studied the effects of physiological levels of PCSK9 on intestinal triglyceride-rich apoB lipoprotein production and elucidated for the first time the cellular and molecular mechanisms involved. Methods and Results - Treatment of human enterocytes (CaCo-2 cells) with recombinant human PCSK9 (10 μg/mL for 24 hours) increased cellular and secreted apoB48 and apoB100 by 40% to 55% each (P

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