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
1   Section of Thrombosis Research
2   Section of Hematology/Oncology, Department of Medicine
,
Miguel A. Cruz
1   Section of Thrombosis Research
,
Khatira Aboulfatova
1   Section of Thrombosis Research
,
Cecilia Martin
1   Section of Thrombosis Research
,
Hiuwan Choi
1   Section of Thrombosis Research
,
Angela L. Bergeron
1   Section of Thrombosis Research
,
Sheryl R. Martini
3   Department of Neurology, Baylor College of Medicine and the Michael E. DeBakey VA Medical Center Stroke Program, Houston, Texas, USA
,
Michael H. Kroll
1   Section of Thrombosis Research
2   Section of Hematology/Oncology, Department of Medicine
,
Thomas A. Kent
3   Department of Neurology, Baylor College of Medicine and the Michael E. DeBakey VA Medical Center Stroke Program, Houston, Texas, USA
› Institutsangaben

Financial support: This work was supported by NIH grants HL71895, HL72886, and HD39833. J.F.D is an Established Investigator of the American Heart Association.
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Publikationsverlauf

Received: 20. November 2007

Accepted after major revision: 23. Januar 2008

Publikationsdatum:
07. Dezember 2017 (online)

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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.