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Review
. 2015 Aug;13(4):206-15.
doi: 10.1007/s11914-015-0270-3.

Molecular Mechanisms of Vascular Calcification in Chronic Kidney Disease: The Link between Bone and the Vasculature

Chang Hyun Byon  1 , Yabing Chen
Affiliations
Review

Molecular Mechanisms of Vascular Calcification in Chronic Kidney Disease: The Link between Bone and the Vasculature

Chang Hyun Byon et al. Curr Osteoporos Rep. 2015 Aug.

Abstract

Vascular calcification is highly prevalent in patients with chronic kidney disease (CKD) and increases mortality in those patients. Impaired calcium and phosphate homeostasis, increased oxidative stress, and loss of calcification inhibitors have been linked to vascular calcification in CKD. Additionally, impaired bone may perturb serum calcium/phosphate and their key regulator, parathyroid hormone, thus contributing to increased vascular calcification in CKD. Therapeutic approaches for CKD, such as phosphate binders and bisphosphonates, have been shown to ameliorate bone loss as well as vascular calcification. The precise mechanisms responsible for vascular calcification in CKD and the contribution of bone metabolism to vascular calcification have not been elucidated. This review discusses the role of systemic uremic factors and impaired bone metabolism in the pathogenesis of vascular calcification in CKD. The regulation of the key osteogenic transcription factor Runt-related transcription factor 2 (Runx2) and the emerging role of Runx2-dependent receptor activator of nuclear factor kappa-B ligand (RANKL) in vascular calcification of CKD are emphasized.

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Conflict of interest statement

Conflict of Interest CH Byon and Y Chen both declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Regulation of vascular calcification in CKD. Impaired calcium/phosphate homeostasis (Ca/Pi), increased oxidative stress, and loss of calcification inhibitors promote vascular calcification in CKD. In addition, increased PTH induces calcium/phosphate release by bone in CKD patients, resulting in severe hyperphosphatemia. High calcium/phosphate, PTH, FGF23, and increased oxidative stress induce the expression of osteogenic transcription factor Runx2, which promotes osteogenic differentiation of VSMC that leads to vascular calcification. Loss of calcification inhibitors, including fetuin-A and pyrophosphate, further enhances VSMC calcification. Upregulation of Runx2 in VSMC induces the expression of RANKL, which in turn may directly enhance VSMC calcification and contribute to bone loss via bone-resorbing osteoclasts. Additionally, VSMC-expressed RANKL promotes migration, cytokine production, and osteoclast formation of macrophages (MØ), which may further accelerate vascular calcification
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