Transient receptor potential melastatin 7 cation channel, magnesium and cell metabolism in vascular health and disease

Abstract

Preserving the balance of metabolic processes in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), is crucial for optimal vascular function and integrity. ECs are metabolically active and depend on aerobic glycolysis to efficiently produce energy for their essential functions, which include regulating vascular tone. Impaired EC metabolism is linked to endothelial damage, increased permeability and inflammation. Metabolic alterations in VSMCs also contribute to vascular dysfunction in atherosclerosis and hypertension. Magnesium (Mg²⁺) is the second most abundant intracellular divalent cation and influences molecular processes that regulate vascular function, including vasodilation, vasoconstriction, and release of vasoactive substances. Mg²⁺ is critically involved in maintaining cellular homeostasis and metabolism since it is an essential cofactor for ATP, nucleic acids and hundreds of enzymes involved in metabolic processes. Low Mg²⁺ levels have been linked to endothelial dysfunction, increased vascular tone, vascular inflammation and arterial remodeling. Growing evidence indicates an important role for the transient receptor potential melastatin-subfamily member 7 (TRPM7) cation channel in the regulation of Mg²⁺ homeostasis in EC and VSMCs. In the vasculature, TRPM7 deficiency leads to impaired endothelial function, increased vascular contraction, phenotypic switching of VSMCs, inflammation and fibrosis, processes that characterize the vascular phenotype in hypertension. Here we provide a comprehensive overview on TRPM7/Mg²⁺ in the regulation of vascular function and how it influences EC and VSMC metabolism such as glucose and energy homeostasis, redox regulation, phosphoinositide signaling, and mineral metabolism. The putative role of TRPM7/Mg²⁺ and altered cellular metabolism in vascular dysfunction and hypertension is also discussed.