Magnesium prevents phosphate-induced calcification in human aortic vascular smooth muscle cells
Open Access
- 9 December 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Nephrology Dialysis Transplantation
- Vol. 28 (4), 869-878
- https://doi.org/10.1093/ndt/gfs520
Abstract
Vascular calcification (VC) is prevalent in patients suffering from chronic kidney disease. Factors promoting calcification include abnormalities in mineral metabolism, particularly high phosphate levels. Inorganic phosphate (Pi) is a classical inducer of in vitro VC. Recently, an inverse relationship between serum magnesium concentrations and VC has been reported. The present study aimed to investigate the effects of magnesium on Pi-induced VC at the cellular level using primary HAVSMC. Alive and fixed HAVSMC were assessed during 14 days in the presence of Pi with increasing concentrations of magnesium (Mg2+) chloride. Mineralization was measured using quantification of calcium, von Kossa and alizarin red stainings. Cell viability and secretion of classical VC markers were also assessed using adequate tests. Involvement of transient receptor potential melastatin (TRPM) 7 was assessed using 2-aminoethoxy-diphenylborate (2-APB) inhibitor. Co-incubation with Mg2+ significantly decreased Pi-induced VC in live HAVSMC, no effect was found in fixed cells. At potent concentrations in Pi-induced HAVSMC, Mg2+ significantly improved cell viability and restored to basal level increased secretions of osteocalcin and matrix gla protein, whereas a decrease in osteopontin secretion was partially restored. The block of TRPM7 with 2-APB at 10−4 M led to the inefficiency of Mg2+ to prevent VC. Increasing Mg2+ concentrations significantly reduced VC, improved cell viability and modulated secretion of VC markers during cell-mediated matrix mineralization clearly pointing to a cellular role for Mg2+ and 2-APB further involved TRPM7 and a potential Mg2+ entry to exert its effects. Further investigations are needed to shed light on additional cellular mechanism(s) by which Mg2+ is able to prevent VC.This publication has 49 references indexed in Scilit:
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