title: Magnesium maintains endothelial integrity, up-regulates proteolysis of ultra-large von Willebrand factor, and reduces platelet aggregation under flow conditions.
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 MgSO(4) 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/cm(2). Release and cleavage of ULVWF by ADAMTS-13 was measured in the absence or presence of physiological or therapeutic levels of MgSO(4). Whole blood or plasma-free reconstituted blood was perfused over immobilized collagen to measure the effect of MgSO(4) on platelet adhesion and aggregation. Also studied were the effects of MgSO(4) on ristocetin-induced platelet aggregation andVWF-collagen interaction. Maintenance of endothelial integrity required physiological levels of MgSO(4), but exogenous MgSO(4) showed no additional benefits. Exogenous MgSO(4) 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. MgSO(4) 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.
authors.affiliation: Section of Thrombosis Research, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. jfdong@bcm.tmc.edu
authors.forename: Jing-fei
authors.initials: JF
authors.lastname: Dong
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Cruz
authors.forename: Khatira
authors.initials: K
authors.lastname: Aboulfatova
authors.forename: Cecilia
authors.initials: C
authors.lastname: Martin
authors.forename: Hiuwan
authors.initials: H
authors.lastname: Choi
authors.forename: Angela L
authors.initials: AL
authors.lastname: Bergeron
authors.forename: Sheryl R
authors.initials: SR
authors.lastname: Martini
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kroll
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kent
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D018929:Cell Culture Techniques; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D018056:Hemorheology; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008278:Magnesium Sulfate / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D013314:Stress, Mechanical; D013997:Time Factors; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D005343:Fibrinolytic Agents; D014841:von Willebrand Factor; D008278:Magnesium Sulfate; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human; D008274:Magnesium