WNT Signaling in Cardiac and Vascular Disease

Sebastien Foulquier, Evangelos P. Daskalopoulos, Gentian Lluri, Kevin C. M. Hermans, Arjun Deb, W. Matthijs Blankesteijn*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

157 Citations (Web of Science)
6 Downloads (Pure)

Abstract

WNT signaling is an elaborate and complex collection of signal transduction pathways mediated by multiple signalingmolecules. WNT signaling is critically important for developmental processes, including cell proliferation, differentiation and tissue patterning. Little WNT signaling activity is present in the cardiovascular system of healthy adults, but reactivation of the pathway is observed in many pathologies of heart and blood vessels. The high prevalence of these pathologies and their significant contribution to human disease burden has raised interest in WNT signaling as a potential target for therapeutic intervention. In this review, we first will focus on the constituents of the pathway and their regulation and the different signaling routes. Subsequently, the role of WNT signaling in cardiovascular development is addressed, followed by a detailed discussion of its involvement in vascular and cardiac disease. After highlighting the crosstalk between WNT, transforming growth factor-beta and angiotensin II signaling, and the emerging role of WNT signaling in the regulation of stem cells, we provide an overview of drugs targeting the pathway at different levels. From the combined studies we conclude that, despite the sometimes conflicting experimental data, a general picture is emerging that excessive stimulation of WNT signaling adversely affects cardiovascular pathology. The rapidly increasing collection of drugs interfering at different levels of WNT signaling will allow the evaluation of therapeutic interventions in the pathway in relevant animal models of cardiovascular diseases and eventually in patients in the near future, translating the outcomes of the many preclinical studies into a clinically relevant context.
Original languageEnglish
Pages (from-to)68-141
Number of pages74
JournalPharmacological Reviews
Volume70
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • MESENCHYMAL STEM-CELLS
  • PULMONARY ARTERIAL-HYPERTENSION
  • GLYCOGEN-SYNTHASE KINASE-3
  • SMALL-MOLECULE INHIBITORS
  • WNT/BETA-CATENIN PATHWAY
  • FRIZZLED-RELATED PROTEIN-1
  • RECEPTOR-RELATED PROTEIN-5
  • SMOOTH-MUSCLE-CELLS
  • RIGHT-VENTRICULAR CARDIOMYOPATHY
  • ENDOTHELIAL GROWTH-FACTOR
  • Humans
  • Wnt Signaling Pathway/drug effects
  • Molecular Targeted Therapy
  • Animals
  • Cardiovascular Diseases/drug therapy

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