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    Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering

    Access Status
    Open access via publisher
    Authors
    Norata, Giuseppe
    Tavori, H.
    Pirillo, A.
    Fazio, S.
    Catapano, A.
    Date
    2016
    Type
    Journal Article
    
    Metadata
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    Citation
    Norata, G. and Tavori, H. and Pirillo, A. and Fazio, S. and Catapano, A. 2016. Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering. Cardiovascular Research. 112 (1): pp. 429-442.
    Source Title
    Cardiovascular Research
    DOI
    10.1093/cvr/cvw194
    ISSN
    0008-6363
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/55517
    Collection
    • Curtin Research Publications
    Abstract

    © 2016 The Author. Proprotein convertase subtilisin kexin 9 (PCSK9) is a key regulator of low-density lipoprotein receptor levels and LDL-cholesterol levels. Loss-of-function mutations in PCSK9 gene are associated with hypocholesterolaemia and protection against cardiovascular disease, identifying PCSK9 inhibition as a valid therapeutic approach to manage hypercholesterolaemia and related diseases. Although PCSK9 is expressed mainly in the liver, it is present also in other tissues and organs with specific functions, raising the question of whether a pharmacological inhibition of PCSK9 to treat hypercholesterolaemia and associated cardiovascular diseases might be helpful or deleterious in non-hepatic tissues. For example, PCSK9 is expressed in the vascular wall, in the kidneys, and in the brain, where it was proposed to play a role in development, neurocognitive process, and neuronal apoptosis. A link between PCSK9 and immunity was also proposed as both sepsis and viral infections are differentially affected in the presence or absence of PCSK9. Despite the increasing number of observations, the debate on the exact roles of PCSK9 in extrahepatic tissues is still ongoing, and as very effective drugs that inhibit PCSK9 have become available to the clinician, a better understanding of the biological roles of PCSK9 is warranted.

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