Vascular Bmp Msx2 Wnt signaling and oxidative stress in arterial calcification.
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.
Washington University School of Medicine, Department of Medicine, Center for Cardiovascular Research, Division of Bone and Mineral Diseases, St. Louis, Missouri 63110, USA.
Jian-Su
JS
Shao
Ziyad Al
ZA
Aly
Chung-Fang
CF
Lai
Su-Li
SL
Cheng
Jun
J
Cai
Emily
E
Huang
Abe
A
Behrmann
Dwight A
DA
Towler
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D008954:Models, Biological; D010012:Osteogenesis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D051153:Wnt Proteins / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D017382:Reactive Oxygen Species; D051153:Wnt Proteins