Metabolic reprogramming in atherosclerosis: Opposed interplay between the canonical WNT/β-catenin pathway and PPARγ

J Mol Cell Cardiol. 2019 Aug:133:36-46. doi: 10.1016/j.yjmcc.2019.05.024. Epub 2019 May 30.

Abstract

Atherosclerosis, a chronic inflammatory and age-related disease, is a complex mechanism presenting a dysregulation of vessel structures. During this process, the canonical WNT/β-catenin pathway is increased whereas PPARγ is downregulated. The two systems act in an opposite manner. This paper reviews the opposing interplay of these systems and their metabolic-reprogramming pathway in atherosclerosis. Activation of the WNT/β-catenin pathway enhances the transcription of targets involved in inflammation, endothelial dysfunction, the proliferation of vascular smooth muscle cells, and vascular calcification. This complex mechanism, which is partly controlled by the WNT/β-catenin pathway, presents several metabolic dysfunctions. This phenomenon, called aerobic glycolysis (or the Warburg effect), consists of a shift in ATP production from mitochondrial oxidative phosphorylation to aerobic glycolysis, leading to the overproduction of intracellular lactate. This mechanism is partially due to the injury of mitochondrial respiration and an increase in the glycolytic pathway. In contrast, PPARγ agonists downregulate the WNT/β-catenin pathway. Therefore, the development of therapeutic targets, such as PPARγ agonists, for the treatment of atherosclerosis could be an interesting and innovative way of counteracting the canonical WNT pathway.

Keywords: Aerobic glycolysis; Atherosclerosis; PPAR gamma; WNT pathway; Warburg effect.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / etiology*
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Biomarkers
  • Cellular Reprogramming*
  • Disease Susceptibility
  • Endothelium / metabolism
  • Energy Metabolism*
  • Extracellular Matrix / metabolism
  • Humans
  • Metabolic Networks and Pathways
  • PPAR gamma / metabolism
  • Protein Binding
  • Vascular Calcification / metabolism
  • Vascular Calcification / pathology
  • Wnt Signaling Pathway

Substances

  • Biomarkers
  • PPAR gamma