Magnesium used in bioabsorbable stents controls smooth muscle cell proliferation and stimulates endothelial cells in vitro

Abstract

Magnesium-based bioabsorbable cardiovascular stents have been developed to overcome limitations of permanent metallic stents, such as late stent thrombosis. During stent degradation, endothelial and smooth muscle cells will be exposed to locally high magnesium concentrations with yet unknown physiological consequences. Here, we investigated the effects of elevated magnesium concentrations on human coronary artery endothelial and smooth muscle cell (HCAEC, HCASMC) growth and gene expression. In the course of 24 h after incubation with magnesium chloride solutions (1 or 10 mM) intracellular magnesium level in HCASMC raised from 0.55 ± 0.25 mM (1 mM) to 1.38 ± 0.95 mM (10 mM), while no increase was detected in HCAEC. Accordingly, a DNA microarray-based study identified 69 magnesium regulated transcripts in HCAEC, but 2172 magnesium regulated transcripts in HCASMC. Notably, a significant regulation of various growth factors and extracellular matrix components was observed. In contrast, viability and proliferation of HCAEC were increased at concentrations of up to 25 mM magnesium chloride, while in HCASMC viability and proliferation appeared to be unaffected. Taken together, our data indicate that magnesium halts smooth muscle cell proliferation and stimulates endothelial cell proliferation, which might translate into a beneficial effect in the setting of stent associated vascular injury.

Microstructure-modified biodegradable magnesium alloy for promoting cytocompatibility and wound healing in vitro

“…ions) can be gradually reused as required mineral nutrients for body supplement. Several studies have investigated the effects of Mg ions on in vitro cell behavior, and reported the Mg ion-induced promoting effect on the proliferation rate of osteoblasts, endothelial cells and fibroblasts [12][13][14]. Furthermore, Mg and other biocompatible metal ions (e.g.…”

Magmaris: a new generation metallic sirolimus-eluting fully bioresorbable scaffold: present status and future perspectives

“…In vitro tests of Mg based BRS showed a decreased smooth muscle cell proliferation and an increased endothelial cell proliferation (33).…”

In vitro and in vivo cytocompatibility evaluation of biodegradable magnesium-based stents: a review

“…In contrast, there was no stimulating effect of the Mg 2+ ions for SMCs [25,51,80,81]. This has been traced down to cell cycle regulation and proliferation-associated genes, which showed only minor changes in ECs but were down-regulated in SMCs, indicating that Mg inhibits SMC proliferation without a major influence on EC proliferation [25,82].…”

“…Besides this, there should be also no or only mild inflammatory reaction during the implantation period. In terms of biodegradable Mg-based stents, relatively high concentrations of Mg ions are released inevitably, thus the influence of the released Mg ions on these cells is necessary to be assessed in in vitro tests [25,26].…”