Effects of low-molecular-weight heparin on adhesion and vesiculation of phospholipid membranes: a possible mechanism for the treatment of hypercoagulability in antiphospholipid syndrome.
Heparins represent an efficient treatment of acute thrombosis and obstetric complications in antiphospholipid syndrome (APS). Enhanced microvesiculation of cell membranes, as detected by reduced membrane adhesion, can contribute to hypercoagulability in APS. Healthy donor IgG antibodies significantly increased beta2-glycoprotein I (beta2-GPI)-induced membrane adhesion, indicating that IgG antibodies might supplement the role of beta2-GPI in the regulation of membrane microvesiculation in healthy individuals. Anti-beta2-GPI IgG antibodies significantly reduced beta2-GPI-induced membrane adhesion, suggesting a direct role of anti-beta2-GPI antibodies in enhancing membrane microvesiculation in APS. Therapeutic concentration of nadroparin completely restored beta2-GPI-induced membrane adhesion in the presence of anti-beta2-GPI IgG antibodies. A novel anticoagulant mechanism of nadroparin in APS is suggested that supplements its direct effect on the coagulation cascade. Restoration of adhesion between negatively charged membranes in the presence of nadroparin might decrease shedding of microvesicles into the surrounding solution and could thus contribute to the efficacy of heparin treatment in APS.
Frank
Mojca
M
Department of Rheumatology, University Medical Center, Ljubljana, Slovenia.
Sodin-Semrl
Snezna
S
Rozman
Blaz
B
Potocnik
Marko
M
Kralj-Iglic
Veronika
V
D000327:Adsorption / Q000187:drug effects; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D008561:Membrane Fusion / Q000187:drug effects; D008563:Membrane Lipids / Q000737:chemistry*; D017762:Nadroparin / Q000737:chemistry / Q000494:pharmacology; D010718:Phosphatidylserines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D053482:beta 2-Glycoprotein I / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D001323:Autoantibodies; D006495:Heparin, Low-Molecular-Weight; D007074:Immunoglobulin G; D008563:Membrane Lipids; D017762:Nadroparin; D010718:Phosphatidylserines; D010743:Phospholipids; D053482:beta 2-Glycoprotein I