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Papers of the Week

2019 Sep 18

Adv Sci (Weinh)



Magnesium Regulates Endothelial Barrier Functions through TRPM7, MagT1, and S1P1.


Zhu D, You J, Zhao N, Xu H
Adv Sci (Weinh). 2019 Sep 18; 6(18):1901166.
PMID: 31559137.


Mg-deficiency is linked to hypertension, Alzheimer's disease, stroke, migraine headaches, cardiovascular diseases, and diabetes, etc., but its exact role in these pathophysiological conditions remains elusive. Mg can regulate vascular functions, yet the mechanistic insight remains ill-defined. Data show that extracellular Mg enters endothelium mainly through the TRPM7 channel and MagT1 transporter. Mg can act as an antagonist to reduce Ca signaling in endothelium. Mg also reduces the intracellular reactive oxygen species (ROS) level and inflammation. In addition, Mg-signaling increases endothelial survival and growth, adhesion, and migration. Endothelial barrier integrity is significantly enhanced with Mg-treatment through S1P1-Rac1 pathways and barrier-stabilizing mediators including cAMP, FGF1/2, and eNOS. Mg also promotes cytoskeletal reorganization and junction proteins to tighten up the barrier. Moreover, Mg-deficiency enhances endothelial barrier permeability in mice, and Mg-treatment rescues histamine-induced transient vessel hyper-permeability in vivo. In summary, Mg-deficiency can cause deleterious effects in endothelium integrity, and Mg-treatment may be effective in the prevention or treatment of vascular dysfunction.