The Interplay of WNT and PPARγ Signaling in Vascular Calcification

Stefan Reinhold, W. Matthijs Blankesteijn, Sebastien Foulquier*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

5 Citations (Web of Science)
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Abstract

Vascular calcification (VC), the ectopic deposition of calcium phosphate crystals in the vessel wall, is one of the primary contributors to cardiovascular death. The pathology of VC is determined by vascular topography, pre-existing diseases, and our genetic heritage. VC evolves from inflammation, mediated by macrophages, and from the osteochondrogenic transition of vascular smooth muscle cells (VSMC) in the atherosclerotic plaque. This pathologic transition partly resembles endochondral ossification, involving the chronologically ordered activation of the beta-catenin-independent and -dependent Wingless and Int-1 (WNT) pathways and the termination of peroxisome proliferator-activated receptor gamma (PPAR gamma) signal transduction. Several atherosclerotic plaque studies confirmed the differential activity of PPAR gamma and the WNT signaling pathways in VC. Notably, the actively regulated beta-catenin-dependent and -independent WNT signals increase the osteochondrogenic transformation of VSMC through the up-regulation of the osteochondrogenic transcription factors SRY-box transcription factor 9 (SOX9) and runt-related transcription factor 2 (RUNX2). In addition, we have reported studies showing that WNT signaling pathways may be antagonized by PPAR gamma activation via the expression of different families of WNT inhibitors and through its direct interaction with beta-catenin. In this review, we summarize the existing knowledge on WNT and PPAR gamma signaling and their interplay during the osteochondrogenic differentiation of VSMC in VC. Finally, we discuss knowledge gaps on this interplay and its possible clinical impact.

Original languageEnglish
Article number2658
Number of pages27
JournalCells
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 2020

Keywords

  • vascular calcification
  • inflammation
  • vascular smooth muscle cells
  • macrophages
  • atherosclerosis
  • cardiovascular disease
  • PPAR&#947
  • WNT
  • &#946
  • -catenin
  • SMOOTH-MUSCLE-CELLS
  • ACTIVATED RECEPTOR-GAMMA
  • MESENCHYMAL STEM-CELLS
  • CORONARY-ARTERY CALCIFICATION
  • CHONDROCYTE DIFFERENTIATION
  • INFLAMMATORY CYTOKINES
  • TRANSCRIPTION FACTORS
  • TNF-ALPHA
  • OSTEOBLAST DIFFERENTIATION
  • DOWN-REGULATION

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