Relationship between Magnesium and Clinical Biomarkers on Inhibition of Vascular Calcification

Abstract

Background: Arteriosclerosis and cardiovascular disease are strongly associated with vascular calcification. Hyperphosphatemia is an essential risk factor for increased vascular calcification. End-stage renal disease (ESRD) patients could serve as an in vivo model for accelerated calcification. This study focuses on the most likely protective effects of magnesium ion (Mg²⁺) on phosphate-induced vascular calcification ex vivo/in vitro. Furthermore, plasma Mg²⁺ concentrations of ESRD and healthy controls were investigated for association with surrogate parameters of vascular calcification in vivo. Methods: Aortic segments of male Wistar-Kyoto rats were incubated and the phosphate concentration of the medium was elevated. The aortic segments were incubated in the absence and presence of MgCl₂; tissue calcification was quantified by different methods. Serum Mg²⁺ concentrations of patients with chronic kidney disease (CKD stage 5; ESRD) and patients without CKD (controls) were associated with carotid intima media thickness (IMT) and aortic pulse wave velocity (PWV) as surrogate parameter for arteriosclerosis and arterial stiffening. Results: Incubation of aortic segments in the presence of β-glycerophosphate and NaH₂PO₄ caused an increased tissue Ca²⁺ deposition compared to control conditions. This increased amount of Ca²⁺ in the aortic rings was significantly decreased in the presence of Mg²⁺. In CKD patients, but not in controls, magnesium serum concentration was associated with the IMT of the carotid arteries. In addition, CKD patients with higher magnesium serum concentration had a significantly lower PWV. Discussion and Conclusion: Elevated phosphate concentrations in the culture media induce ex vivo/in vitro medial calcification in intact rat aortic rings in the presence of alkaline phosphatase. Mg²⁺ ions reduced ex vivo/in vitro vascular calcification despite increased phosphate concentration. This hypothesis is additionally based on the fact that CKD patients with high Mg² serum levels had significantly lower IMT and PWV values, which may result in a lower risk for cardiovascular events and mortality in these patients. Therefore, Mg²⁺ supplementation may be an option for treatment and prevention of vascular calcification resulting in a reduction of cardiovascular events in CKD patients.