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
  • Ter braake, Anique D, Radboud University Medical Center, Nijmegen, Netherlands
  • Bindels, René J., Radboud University Medical Center, Nijmegen, Netherlands
  • Hoenderop, Joost, Radboud University Medical Center, Nijmegen, Netherlands
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.