Magnesium deficiency impairs human microvascular endothelial cell function by silencing TRPM7

Evidence has accumulated to suggest that magnesium might play a role in controlling angiogenesis. Since microvascular endothelial cells are protagonists in this process, we investigated the behavior of these cells cultured in low extracellular magnesium. In particular, we focused on some crucial steps of the angiogenic process, i.e. proliferation, migration, protease production and organization in tridimensional structures. We found that while low extracellular magnesium has no effects on the production of metalloproteases and on tridimensional organization on matrigel, it impairs cell migration and inhibits growth by arresting the cells in the G0/G1 and G2/M phases of the cell cycle. Since in human microvascular endothelial cells i) low extracellular magnesium markedly decreases the amounts of the magnesium transporter Transient Receptor Potential Melastatin (TRPM)7, which is essential for magnesium homeostasis at the cellular level, and ii) silencing TRPM7 mimics the effects of low extracellular magnesium, we suggest that TRPM7 downregulation mediates low magnesium-induced inhibition of cell growth and migration. It is noteworthy that also endothelial colony-forming cells, which contribute to new vessel formation, are sensitive to fluctuations of the concentrations of extracellular magnesium. Our results point to magnesium and TRPM7 as a modulators of angiogenic properties of microvacular endothelial cells and endothelial colony-forming cells.