Magnesium Supplementation Attenuates Pulmonary Hypertension via Regulation of Magnesium Transporters

Pulmonary hypertension (PH) is characterized by profound vascular remodeling and altered Ca 2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Magnesium ion (Mg ), a natural antagonist cofactor for numerous enzymes, crucial regulating diverse cellular functions, but its roles PH remains unclear. Here, we examined the of Mg transporters development. Chronic hypoxia monocrotaline induced significant adult male rats. It was associated with reduction [Mg ] i PASMCs, increase gene expressions Cnnm2 , Hip14 Hip14l Magt1 Mmgt1 Mrs2 Nipa1 Nipa2 Slc41a1 Slc41a2 Trpm7 ; upregulation SLC41A1, SLC41A2, CNNM2, TRPM7 proteins; downregulation SLC41A3 mRNA protein. supplement attenuated pressure, right heart hypertrophy, medial wall thickening arteries, reversed changes expression transporters. Incubation PASMCs high concentration markedly inhibited PASMC proliferation migration, increased apoptosis, whereas low level produced opposite effects. siRNA targeting Slc41a1/2, Cnnm2, promoted apoptosis; Slc41a3 overexpression also caused similar Moreover, or incubation hypoxia-induced nuclear translocation NFATc3 PASMCs. The results, first time, provide supportive evidence that participate development modulating proliferation, supplementation attenuates through regulation involving signaling pathway.