Calciprotein particle inhibition explains magnesiummediated protection against vascular calcification

Ter Braake, A. D., Eelderink, C., Zeper, L. W., Pasch, A., Bakker, S. J. L., de Borst, M. H., Hoenderop, J. G. J. & de Baaij, J. H. F., May-2020, In : Nephrology Dialysis Transplantation. 35, 5, p. 765-773 9 p., gfz190.

Research output: Contribution to journalArticleAcademicpeer-review

BACKGROUND: Phosphate (Pi) toxicity is a strong determinant of vascular calcification development in chronic kidney disease (CKD). Magnesium (Mg2+) may improve cardiovascular risk via vascular calcification. The mechanism by which Mg2+ counteracts vascular calcification remains incompletely described. Here we investigated the effects of Mg2+ on Pi and secondary crystalline calciprotein particles (CPP2)-induced calcification and crystal maturation.

METHODS: Vascular smooth muscle cells (VSMCs) were treated with high Pi or CPP2 and supplemented with Mg2+ to study cellular calcification. The effect of Mg2+ on CPP maturation, morphology and composition was studied by medium absorbance, electron microscopy and energy dispersive spectroscopy. To translate our findings to CKD patients, the effects of Mg2+ on calcification propensity (T50) were measured in sera from CKD patients and healthy controls.

RESULTS: Mg2+ supplementation prevented Pi-induced calcification in VSMCs. Mg2+ dose-dependently delayed the maturation of primary CPP1 to CPP2 in vitro. Mg2+ did not prevent calcification and associated gene and protein expression when added to already formed CPP2. Confirmatory experiments in human serum demonstrated that the addition of 0.2 mmol/L Mg2+ increased T50 from healthy controls by 51 ± 15 min (P < 0.05) and CKD patients by 44 ± 13 min (P < 0.05). Each further 0.2 mmol/L addition of Mg2+ led to further increases in both groups.

CONCLUSIONS: Our results demonstrate that crystalline CPP2 mediates Pi-induced calcification in VSMCs. In vitro, Mg2+ delays crystalline CPP2 formation and thereby prevents Pi-induced calcification.

Original languageEnglish
Article numbergfz190
Pages (from-to)765-773
Number of pages9
JournalNephrology Dialysis Transplantation
Issue number5
Early online date12-Oct-2019
Publication statusPublished - May-2020

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