Kidney Week

Abstract: SA-PO851

Magnesium Prevents Vascular Calcification by Inhibition of Hydroxyapatite Crystal Formation

Session Information

• Vascular Calcification
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Mineral Disease

• 1205 Vascular Calcification

Authors

• De Baaij, Jeroen H.F., Radboud University Medical Center, Nijmegen, Netherlands

Jeroen H.F. De Baaij,

• Ter braake, Anique D, Radboud University Medical Center, Nijmegen, Netherlands

Anique D Ter braake,

• Bindels, René J., Radboud University Medical Center, Nijmegen, Netherlands

René J. Bindels,

• Hoenderop, Joost, Radboud University Medical Center, Nijmegen, Netherlands

Joost Hoenderop,

Background

Mg²⁺ has been shown to effectively prevent vascular calcification in multiple experimental calcification models. Vascular calcification is common in chronic kidney disease and contributes to increased mortality. Mg²⁺ has been hypothesized to prevent the upregulation of osteoblastic gene expression that drive calcification. However, extracellular effects of Mg²⁺ on Ca²⁺-Pi crystal formation have been largely neglected. This study aimed to investigate the effects of Mg²⁺ on both intracellular changes associated with vascular calcification as well as effects on crystal formation in the extracellular space.

Methods

Bovine vascular smooth muscle cells (bVSMC) were calcified using β-glycerophosphate (BGP). Transdifferentiation was assessed by transcriptional analysis, cellular alkaline phosphatase (ALP) activity and development of apoptosis. X-ray powder diffraction, scanning electron microscopy and energy dispersive spectroscopy on crystals isolated from cell culture supernatants were used to map extracellular effects of Mg²⁺ on crystal formation and crystal composition.

Results

Mg²⁺ effectively prevented BGP-induced calcification in bVSMC. BGP did not cause changes in mRNA expression of the osteogenic genes BMP2, RUNX2 or ALP. Moreover, alkaline phosphatase activity was stable and apoptosis was only detected after calcification independent of Mg²⁺. In addition, blocking of the Mg²⁺ channel TRPM7 using 2-ABP did not abrogate the protective effects of Mg²⁺, indicating that intracellular Mg²⁺ is not involved in BGP-induced calcification of bVSMCs. Extracellular Mg²⁺ prevented the formation of hydroxyapatite crystals, which formed extensively after BGP treatment. Further analysis of the composition of the hydroxyapatite crystals showed that Mg²⁺ supplementation resulted in reduced Ca²⁺ and Pi fractions of 68% and 41%, respectively, without increasing the fraction of Mg²⁺.

Conclusion

This study demonstrates that Mg²⁺ inhibits bVSMC mineralization through inhibition of Ca²⁺-apatite formation in the extracellular space, independent of VSMC transdifferentiation. These results emphasize the need for randomized-controlled clinical trials assessing the effects of Mg²⁺ supplementation on vascular calcification.

Funding

• Government Support - Non-U.S.