Vascular Bmp-Msx2-Wnt signaling and oxidative stress in arterial calcification

Jian Su Shao, Ziyad Al Aly, Chung Fang Lai, Su Li Cheng, Jun Cai, Emily Huang, Abe Behrmann, Dwight A. Towler

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Studies of fracture repair have revealed that paracrine endothelial-mesenchymal interactions direct bone formation that restores osseous integrity. Angiogenic growth factors and specific members of the bone morphogenetic protein (BMP) family mediate these interactions. Recently, these same signals have been shown to be critical in the vascular pathobiology of hypertension, diabetes, and atherosclerosis. In the arterial vasculature, mechanical and inflammatory redox signals, characteristic of hypertension and diabetes have emerged as a secretagogues for BMP production - with downstream activation of endothelial NADPH oxidases (Nox). Preliminary data now indicate that the paracrine signals provided by BMP and reactive oxygen species augment aortic myofibroblast Msx2-Wnt signaling and matrix turnover. The net mural response to these stimuli promotes osteogenic differentiation of calcifying vascular cells, moreover, oxidation of vascular LDL cholesterol generates oxysterols that trigger Runx2 activity via hedgehog pathways. Thus, BMP, Wnt, and hedgehog gene expression programs - osteogenic pathways highly familiar to the bone biologist - are elaborated in the arterial vasculature via redox-regulated mechanisms. In the brief review, we recount mounting evidence that points to oxidative stress as a major contributor to the pathobiology of diabetic arterial calcification.

Original languageEnglish (US)
Pages (from-to)40-50
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume1117
DOIs
Publication statusPublished - Nov 1 2007

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Keywords

  • Aorta
  • Diabetes
  • Inflammation
  • Medial artery calcification
  • Oxidative stress
  • Peripheral vascular disease
  • Vascular calcification
  • Wnt signaling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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