IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v3y2012i1d10.1038_ncomms2087.html
   My bibliography  Save this article

The nuclear hormone receptor PPARγ counteracts vascular calcification by inhibiting Wnt5a signalling in vascular smooth muscle cells

Author

Listed:
  • Estelle Woldt

    (CNRS, UMR 7213, University of Strasbourg)

  • Jérome Terrand

    (CNRS, UMR 7213, University of Strasbourg)

  • Mohamed Mlih

    (CNRS, UMR 7213, University of Strasbourg)

  • Rachel L. Matz

    (CNRS, UMR 7213, University of Strasbourg)

  • Véronique Bruban

    (CNRS, UMR 7213, University of Strasbourg)

  • Fanny Coudane

    (CNRS, UMR 7213, University of Strasbourg)

  • Sophie Foppolo

    (CNRS, UMR 7213, University of Strasbourg)

  • Zeina El Asmar

    (CNRS, UMR 7213, University of Strasbourg)

  • Maria Eugenia Chollet

    (INSERM UMRS937, University of Paris)

  • Ewa Ninio

    (INSERM UMRS937, University of Paris)

  • Audrey Bednarczyk

    (CNRS, UMR 7178, University of Strasbourg)

  • Danièle Thiersé

    (CNRS, UMR 7178, University of Strasbourg)

  • Christine Schaeffer

    (CNRS, UMR 7178, University of Strasbourg)

  • Alain Van Dorsselaer

    (CNRS, UMR 7178, University of Strasbourg)

  • Christian Boudier

    (CNRS, UMR 7213, University of Strasbourg)

  • Walter Wahli

    (Center for Integrative Genomics, University of Lausanne)

  • Pierre Chambon

    (IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Inserm 964/CNRS UMR 7104, University of Strasbourg)

  • Daniel Metzger

    (IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Inserm 964/CNRS UMR 7104, University of Strasbourg)

  • Joachim Herz

    (and Center for Alzheimer's and Neurodegenerative Disease, UT Southwestern Medical Center)

  • Philippe Boucher

    (CNRS, UMR 7213, University of Strasbourg)

Abstract

Vascular calcification is a hallmark of advanced atherosclerosis. Here we show that deletion of the nuclear receptor PPARγ in vascular smooth muscle cells of low density lipoprotein receptor (LDLr)-deficient mice fed an atherogenic diet high in cholesterol, accelerates vascular calcification with chondrogenic metaplasia within the lesions. Vascular calcification in the absence of PPARγ requires expression of the transmembrane receptor LDLr-related protein-1 in vascular smooth muscle cells. LDLr-related protein-1 promotes a previously unknown Wnt5a-dependent prochondrogenic pathway. We show that PPARγ protects against vascular calcification by inducing the expression of secreted frizzled-related protein-2, which functions as a Wnt5a antagonist. Targeting this signalling pathway may have clinical implications in the context of common complications of atherosclerosis, including coronary artery calcification and valvular sclerosis.

Suggested Citation

  • Estelle Woldt & Jérome Terrand & Mohamed Mlih & Rachel L. Matz & Véronique Bruban & Fanny Coudane & Sophie Foppolo & Zeina El Asmar & Maria Eugenia Chollet & Ewa Ninio & Audrey Bednarczyk & Danièle Th, 2012. "The nuclear hormone receptor PPARγ counteracts vascular calcification by inhibiting Wnt5a signalling in vascular smooth muscle cells," Nature Communications, Nature, vol. 3(1), pages 1-10, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2087
    DOI: 10.1038/ncomms2087
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms2087
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms2087?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:3:y:2012:i:1:d:10.1038_ncomms2087. 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.