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

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 Thiersé, Christine Schaeffer, Alain Van Dorsselaer, Christian Boudier, Walter Wahli, Pierre Chambon, Daniel Metzger, Joachim Herz and Philippe Boucher ()
Additional contact information
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

Nature Communications, 2012, vol. 3, issue 1, 1-10

Abstract: 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.

Date: 2012
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DOI: 10.1038/ncomms2087

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