Magnesium maintains endothelial integrity, up-regulates proteolysis of ultra-large von Willebrand factor, and reduces platelet aggregation under flow conditions

Jing-fei Dong; Miguel A. Cruz; Khatira Aboulfatova; Cecilia Martin; Hiuwan Choi; Angela L. Bergeron; Sheryl R. Martini; Michael H. Kroll; Thomas A. Kent

doi:10.1160/TH07-11-0694

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2008; 99(03): 586-593
DOI: 10.1160/TH07-11-0694

Endothelium and Vascular Development

Schattauer GmbH

Magnesium maintains endothelial integrity, up-regulates proteolysis of ultra-large von Willebrand factor, and reduces platelet aggregation under flow conditions

Jing-fei Dong

¹Section of Thrombosis Research

²Section of Hematology/Oncology, Department of Medicine

,

Miguel A. Cruz

¹Section of Thrombosis Research

,

Khatira Aboulfatova

¹Section of Thrombosis Research

,

Cecilia Martin

¹Section of Thrombosis Research

,

Hiuwan Choi

¹Section of Thrombosis Research

,

Angela L. Bergeron

¹Section of Thrombosis Research

,

Sheryl R. Martini

³Department of Neurology, Baylor College of Medicine and the Michael E. DeBakey VA Medical Center Stroke Program, Houston, Texas, USA

,

Michael H. Kroll

¹Section of Thrombosis Research

²Section of Hematology/Oncology, Department of Medicine

,

Thomas A. Kent

³Department of Neurology, Baylor College of Medicine and the Michael E. DeBakey VA Medical Center Stroke Program, Houston, Texas, USA

› Institutsangaben

Abstract

Summary

Mg ⁺⁺ regulates endothelial functions and has anti-inflammatory effects. Its effects on thrombosis have been demonstrated, but the mechanism remains poorly understood.We investigated the roles of MgSO₄ in regulating the release and cleavage of the prothrombotic ultra-large (UL) von Willebrand factor (VWF) and VWF-mediated platelet adhesion and aggregation.Washed platelets were perfused over cultured endothelial cells from human umbilical cord veins under a shear stress of 2.5 dyn/cm². Release and cleavage of ULVWF by ADAMTS-13 was measured in the absence or presence of physiological or therapeutic levels of MgSO₄. Whole blood or plasma-free reconstituted blood was perfused over immobilized collagen to measure the effect of MgSO₄ on platelet adhesion and aggregation. Also studied were the effects of MgSO₄ on ristocetin-induced platelet aggregation andVWF-collagen interaction.Maintenance of endothelial integrity required physiological levels of MgSO₄, but exogenous MgSO₄ showed no additional benefits.Exogenous MgSO₄ significantly enhanced the cleavage of the newly released ULVWF strings by ADAMTS-13 and markedly reduced platelet aggregation on immobilized collagen under flow conditions.This effect is likely to be mediated through VWF as Mg⁺⁺ partially inhibited ristocetin-induced platelet aggregation andVWF binding to collagen.MgSO₄ is critical for maintaining endothelial integrity and regulates ULVWF proteolysis and aggregation under flow conditions. These results provide a new insight into additional mechanisms involved with magnesium therapy.

Keywords

Magnesium - endothelium - platelets - ADAMTS-13

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Referenzen

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