IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-05806-0.html
   My bibliography  Save this article

Apolipoprotein A-IV binds αIIbβ3 integrin and inhibits thrombosis

Author

Listed:
  • Xiaohong Ruby Xu

    (University of Toronto
    St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    Department of Acupuncture and Moxibustion, Guangdong Provincial Hospital of Chinese Medicine
    Guangzhou University of Chinese Medicine)

  • Yiming Wang

    (University of Toronto
    St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    Canadian Blood Services Centre for Innovation)

  • Reheman Adili

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group)

  • Lining Ju

    (Georgia Institute of Technology
    Georgia Institute of Technology
    The University of Sydney)

  • Christopher M. Spring

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group)

  • Joseph Wuxun Jin

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    Canadian Blood Services Centre for Innovation)

  • Hong Yang

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    Canadian Blood Services Centre for Innovation)

  • Miguel A. D. Neves

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group)

  • Pingguo Chen

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    Canadian Blood Services Centre for Innovation)

  • Yan Yang

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    Canadian Blood Services Centre for Innovation)

  • Xi Lei

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group)

  • Yunfeng Chen

    (Georgia Institute of Technology
    Georgia Institute of Technology)

  • Reid C. Gallant

    (University of Toronto
    St. Michael’s Hospital, and Toronto Platelet Immunobiology Group)

  • Miao Xu

    (University of Toronto
    St. Michael’s Hospital, and Toronto Platelet Immunobiology Group)

  • Hailong Zhang

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group)

  • Jina Song

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    Canadian Blood Services Centre for Innovation)

  • Peifeng Ke

    (Guangzhou University of Chinese Medicine
    Guangdong Provincial Hospital of Chinese Medicine)

  • Dan Zhang

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    Guangzhou University of Chinese Medicine)

  • Naadiya Carrim

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    Canadian Blood Services Centre for Innovation)

  • Si-Yang Yu

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    The Second Xiangya Hospital of Central South University)

  • Guangheng Zhu

    (St. Michael’s Hospital, and Toronto Platelet Immunobiology Group)

  • Yi-Min She

    (Biologics and Genetic Therapies Directorate, HPFB, Health Canada)

  • Terry Cyr

    (Biologics and Genetic Therapies Directorate, HPFB, Health Canada)

  • Wenbin Fu

    (Department of Acupuncture and Moxibustion, Guangdong Provincial Hospital of Chinese Medicine
    Guangzhou University of Chinese Medicine)

  • Guoqing Liu

    (Peking University Health Science Center)

  • Philip W. Connelly

    (University of Toronto
    St. Michael’s Hospital, and Toronto Platelet Immunobiology Group)

  • Margaret L. Rand

    (University of Toronto
    Division of Haematology/Oncology, The Hospital for Sick Children)

  • Khosrow Adeli

    (University of Toronto
    The Hospital for Sick Children)

  • John Freedman

    (University of Toronto
    St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    University of Toronto)

  • Jeffrey E. Lee

    (University of Toronto)

  • Patrick Tso

    (University of Cincinnati)

  • Patrizia Marchese

    (The Scripps Research Institute)

  • W. Sean Davidson

    (University of Cincinnati)

  • Shaun P. Jackson

    (The University of Sydney
    The Scripps Research Institute)

  • Cheng Zhu

    (Georgia Institute of Technology
    Georgia Institute of Technology
    Georgia Institute of Technology)

  • Zaverio M. Ruggeri

    (The Scripps Research Institute)

  • Heyu Ni

    (University of Toronto
    St. Michael’s Hospital, and Toronto Platelet Immunobiology Group
    Canadian Blood Services Centre for Innovation
    University of Toronto)

Abstract

Platelet αIIbβ3 integrin and its ligands are essential for thrombosis and hemostasis, and play key roles in myocardial infarction and stroke. Here we show that apolipoprotein A-IV (apoA-IV) can be isolated from human blood plasma using platelet β3 integrin-coated beads. Binding of apoA-IV to platelets requires activation of αIIbβ3 integrin, and the direct apoA-IV-αIIbβ3 interaction can be detected using a single-molecule Biomembrane Force Probe. We identify that aspartic acids 5 and 13 at the N-terminus of apoA-IV are required for binding to αIIbβ3 integrin, which is additionally modulated by apoA-IV C-terminus via intra-molecular interactions. ApoA-IV inhibits platelet aggregation and postprandial platelet hyperactivity. Human apoA-IV plasma levels show a circadian rhythm that negatively correlates with platelet aggregation and cardiovascular events. Thus, we identify apoA-IV as a novel ligand of αIIbβ3 integrin and an endogenous inhibitor of thrombosis, establishing a link between lipoprotein metabolism and cardiovascular diseases.

Suggested Citation

  • Xiaohong Ruby Xu & Yiming Wang & Reheman Adili & Lining Ju & Christopher M. Spring & Joseph Wuxun Jin & Hong Yang & Miguel A. D. Neves & Pingguo Chen & Yan Yang & Xi Lei & Yunfeng Chen & Reid C. Galla, 2018. "Apolipoprotein A-IV binds αIIbβ3 integrin and inhibits thrombosis," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05806-0
    DOI: 10.1038/s41467-018-05806-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-05806-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-05806-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05806-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.