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

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

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 and VWF-collagen interaction. Maintenance of endothelial integrity required physiological levels of MgSO4, but exogenous MgSO 4 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 and VWF 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.

Original languageEnglish (US)
Pages (from-to)586-593
Number of pages8
JournalThrombosis and Haemostasis
Volume99
Issue number3
DOIs
StatePublished - Mar 2008

Keywords

  • ADAMTS-13
  • Endothelium
  • Magnesium
  • Platelets

ASJC Scopus subject areas

  • Hematology

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