Journal of Cell Science & Therapy
Open Access
ISSN: 2157-7013
+44 1300 500008
ISSN: 2157-7013
+44 1300 500008
Philippe Boucher
Scientific Tracks Abstracts: J Cell Sci Ther
V ascular calcification is a hallmark of advanced atherosclerosis, but the underlying mechanisms remain unknown. Here we show that deletion of the nuclear receptor PPARg in vascular smooth muscle cells (vSMCs) of Low Density Lipoprotein receptor (LDLr) deficient mice fed an atherogenic high-cholesterol diet results in accelerated vascular calcification with chondrogenic metaplasia within the lesions. We demonstrate that vascular calcification in the absence of PPARg requires the transmembrane receptor Low Density Lipoprotein receptor-related protein-1 (LRP1) in vSMCs. LRP1 promotes a previously unknown Wnt5a dependent prochondrogenic pathway that activates the chondrogenic program. PPARg ⎕ protects against vascular calcification by inducing the expression of sFRP2, which we show functions as a Wnt5a antagonist. Thus, targeting this signaling pathway has important clinical implications, impacting on common complications of atherosclerosis including coronary artery calcification and valvular sclerosis.
Philippe Boucher is professor of Physiology at University of Strasbourg. After a Ph.D. at the University of Lyon, France and a postdoctoral fellowship at University of Texas, Southwestern Medical Center at Dallas he became an assistant professor of Physiology at University of Strasbourg before moving on a full professor position. His lab aims to understand cell signalling networks and, in more specific terms, how LRP1 and its partners impact on growth-promoting and differentiation signals that protect against disorders such as atherosclerosis, vascular calcification and arthrosis. He has published more than 25 papers in reputed journals. His work has identified several fundamental molecular mechanisms by which these genes protect against atherosclerosis, vascular calcification, and promote cartilage regeneration