Blood Vessels/Endothelium
Dysregulation of vascular TRPM7 and annexin-1 is associated with endothelial dysfunction in inherited hypomagnesemia,

Abstract
Inadequate magnesium intake and hypomagnesemia may contribute to chronic diseases, such as hypertension. The novel magnesium transporter TRPM7 is a critical regulator of magnesium homeostasis in vascular cells, but its role in pathophysiology is unclear. In a model of hypomagnesemia, we examined microvascular structure and function, TRPM7 expression, and vascular inflammatory status using inbred mice selected for normal-high intracellular magnesium levels or low intracellular magnesium levels (MgLs). Blood pressure was significantly increased in MgLs compared with normal-high intracellular magnesium levels. Pressurized myography of mesenteric resistance arteries showed that MgLs had significantly impaired endothelial function together with decreased plasma nitrate levels and endothelial NO synthase expression when compared with normal-high intracellular magnesium levels. Significant differences in vascular structure were also evident in both mesenteric arteries and aortas from MgLs. Aortas from MgLs had increased medial cross-sectional areas, whereas mesenteric arteries from MgLs had increased lumen diameters with increased medial cross-sectional areas, indicating outward hypertrophic remodeling. Expression of the magnesium transporter TRPM7 was significantly elevated in the vasculature of MgLs, whereas expression of a TRPM7 downstream target, the anti-inflammatory molecule annexin-1, was reduced. MgLs had increased expression of vascular cell adhesion molecule-1 and plasminogen activator inhibitor-1, indicating vascular inflammation. Taken together, these data demonstrate that the inherited magnesium status of MgLs and normal-high intracellular magnesium levels mice affects magnesium transporter expression, endothelial function, vascular structure, and inflammation. Our findings suggest a potential regulatory role for TRPM7 signaling in the maintenance of vascular integrity. Alterations in magnesium status and/or TRPM7 signaling may contribute to vascular injury in conditions associated with hypomagnesemia. ...

... Perspectives
Inadequate magnesium intake and hypomagnesemia are widely prevalent in the community and may contribute to the pathophysiology of chronic diseases, such as hypertension. Our data demonstrate that magnesium plays an important role in the maintenance of vascular integrity, with hypomagnesemia exerting detrimental effects on endothelial function, vascular structure, and inflammation. We also demonstrate that the magnesium transporter TRPM7 is upregulated in hypomagnesemia, which may represent a compensatory response. Additional work is required to fully understand the relationships between the complex systems responsible for the regulation of magnesium homeostasis, the role of TRPM7 in vascular signaling, and their impact on the cardiovascular system. Such research has important consequences for understanding and estimating the clinical implications of hypomagnesemia for cardiovascular disease.


Full paper: http://hyper.ahajournals.org/content/53/2/423.long

Inadequate magnesium intake and hypomagnesemia may contribute to chronic diseases, such as hypertension. The novel magnesium transporter TRPM7 is a critical regulator of magnesium homeostasis in vascular cells, but its role in pathophysiology is unclear. In a model of hypomagnesemia, we examined mic…