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Vascular Bmp–Msx2–Wnt Signaling and Oxidative Stress in Arterial Calcification
Author(s) -
SHAO JIANSU,
ALY ZIYAD AL,
LAI CHUNGFANG,
CHENG SULI,
CAI JUN,
HUANG EMILY,
BEHRMANN ABE,
TOWLER DWIGHT A.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1402.075
Subject(s) - paracrine signalling , wnt signaling pathway , microbiology and biotechnology , oxidative stress , calcification , bone morphogenetic protein , chemistry , bone morphogenetic protein 2 , endocrinology , medicine , biology , signal transduction , biochemistry , receptor , gene , in vitro
: 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.