Endothelial-mesenchymal transition in atherosclerotic lesion calcification

Atherosclerosis. 2016 Oct:253:124-127. doi: 10.1016/j.atherosclerosis.2016.08.046. Epub 2016 Sep 2.

Abstract

Background and aims: Endothelial-mesenchymal transitions (EndMTs) in endothelial cells (ECs) contribute to vascular disease.

Methods: We used ApoE-/- mice fed a high-fat/high-cholesterol diet.

Results: We reported evidence of EndMT in atherosclerotic lesions contributing to calcification. Stem cell and mesenchymal markers, including sex-determining region Y-box 2 (Sox2), were upregulated in aortic ECs of fat-fed ApoE-/- mice. Limiting Sox2 decreased marker expression and calcification in ApoE-/- aortas. Furthermore, a complex of serine proteases was upregulated in ApoE-/- aortic ECs. Blockade of these proteases reduced expression of Sox2 and atherosclerotic lesion calcification.

Conclusions: Together, our data suggest that EndMTs contribute to atherosclerotic lesion calcification.

Keywords: Atherosclerotic lesion calcification; Endothelial cells; Endothelial-mesenchymal transition; Serine protease; Sex-determining region Y-box 2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / cytology*
  • Aorta / metabolism
  • Atherosclerosis / blood*
  • Calcinosis / blood*
  • Cholesterol / metabolism
  • Cytokines / metabolism
  • Endothelial Cells / cytology*
  • Endothelium, Vascular / metabolism
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Mice
  • Mice, Knockout, ApoE
  • Plaque, Atherosclerotic / pathology
  • SOXB1 Transcription Factors / genetics*
  • SOXB1 Transcription Factors / metabolism
  • Serine Endopeptidases / metabolism
  • Stem Cells / cytology
  • Up-Regulation

Substances

  • Cytokines
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Cholesterol
  • Serine Endopeptidases