The Nuclear Hormone Receptor PPARγ Counteracts Vascular Calcification by Inhibiting Wnt5a Signalling in Vascular Smooth Muscle Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2012 Sep 27

PMID 23011131

Citations 45

Authors

Estelle Woldt

Jerome Terrand

Mohamed Mlih

Rachel L Matz

Veronique Bruban

Fanny Coudane

Sophie Foppolo

Zeina El Asmar

Maria Eugenia Chollet

Ewa Ninio

Audrey Bednarczyk

Daniele Thierse

Christine Schaeffer

Alain Van Dorsselaer

Christian Boudier

Walter Wahli

Pierre Chambon

Daniel Metzger

Joachim Herz

Philippe Boucher

Affiliations

Soon will be listed here.

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.

Citing Articles

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