GSK3β Inhibition Ameliorates Atherosclerotic Calcification

Int J Mol Sci. 2023 Jul 19;24(14):11638. doi: 10.3390/ijms241411638.

Abstract

Endothelial-mesenchymal transition (EndMT) drives endothelium to contribute to atherosclerotic calcification. In a previous study, we showed that glycogen synthase kinase-3β (GSK3β) inhibition induced β-catenin and reduced mothers against DPP homolog 1 (SMAD1) in order to redirect osteoblast-like cells towards endothelial lineage, thereby reducing vascular calcification in Matrix Gla Protein (Mgp) deficiency and diabetic Ins2Akita/wt mice. Here, we report that GSK3β inhibition or endothelial-specific deletion of GSK3β reduces atherosclerotic calcification. We also find that alterations in β-catenin and SMAD1 induced by GSK3β inhibition in the aortas of Apoe-/- mice are similar to Mgp-/- mice. Together, our results suggest that GSK3β inhibition reduces vascular calcification in atherosclerotic lesions through a similar mechanism to that in Mgp-/- mice.

Keywords: atherosclerosis; glycogen synthase kinase-3β; vascular calcification.

MeSH terms

  • Animals
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / genetics
  • Atherosclerosis* / metabolism
  • Calcification, Physiologic
  • Glycogen Synthase Kinase 3 beta* / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta* / genetics
  • Mice
  • Vascular Calcification* / chemically induced
  • Vascular Calcification* / drug therapy
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse