Vitamin D and osteogenic differentiation in the artery wall

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Abstract

Vascular calcification is widespread, particularly in patients with chronic kidney disease, who receive, among other treatments, active vitamin D supplements. Emerging evidence indicates that vascular calcification is a regulated process that resembles embryonic endochondral osteogenesis, involving osteoblastic differentiation of vascular smooth muscle cells. In experimental animal models, high dosages of vitamin D consistently promote vascular calcification. In particular, the vitamin D-fed rat is frequently used as a model to assess putative regulators of calcific vasculopathy. The artery wall calcification in these animals most likely results from multiple mechanisms involving systems physiology of the complex, bone-vascular-renal-endocrine axis. Genetically engineered mice with upregulated vitamin D signaling pathways have also shed light on the molecular intermediaries, including fibroblast growth factor-23 and transcriptional intermediary factor 1-α. In contrast to the studies of animals, studies of humans show that vitamin D has an inverse relationship or little effect. This difference between in vitro and in vivo findings is most likely, again, due to the complex, systemic feedback regulatory mechanisms that control calcium-phosphate metabolism. Recent epidemiologic evidence suggests that there is a narrow range of vitamin D levels in which vascular function is optimized. Levels above or below this range seem to confer a significant increase in risk for cardiovascular disease. There is some evidence to suggest that dietary vitamin D may be carried by lipoprotein particles into cells of the artery wall and atherosclerotic plaque, where it may be converted to active form by monocyte-macrophages. These findings raise interesting questions regarding the effects of vitamin D intake on atherosclerotic calcification and cardiovascular risk. Copyright © 2008 by the American Society of Nephrology.

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Hsu, J. J., Tintut, Y., & Demer, L. L. (2008). Vitamin D and osteogenic differentiation in the artery wall. Clinical Journal of the American Society of Nephrology, 3(5), 1542–1547. https://doi.org/10.2215/CJN.01220308

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