Antioxidant susceptibility of pathogenic pathways in subjects with antiphospholipid antibodies: a pilot study.
The pathogenesis of antiphospholipid antibody (aPL) related thrombosis is multifactorial and includes, amongst others, enhanced coagulation activation measured as prothrombin fragment 1 + 2 (F1 + 2), elevated plasma levels of von Willebrand factor (vWF), plasminogen activator inhibitor (PAI) and endothelin-1 (ET-1) as well as heightened thromboxane generation and lipid peroxidation. To evaluate the antioxidant susceptibility of some of the above pathways, probucol (500 mg/d orally, a cholesterol lowering agent bearing antioxidant properties) was administered for a three week period to 14 subjects with aPL and to seven healthy controls. At baseline aPL participants showed higher plasma levels of vWF (P = 0.006), ET-1 (P = 0.0002) and enhanced urinary excretion of 11-dehydro-thromboxane-B2 (TXB2) (P = 0.0004), F2-isoprostanes (marker of lipid peroxidation) (P = 0.02) and albumin (P = 0.04) than controls. In the aPL group baseline IgG anticardiolipin (aCL) titre positively related with urinary TXB2 (r2 = 0.43, P = 0.01) and inversely with urinary NOx (r2 = -0.6, P = 0.005) whereas urinary NOx and TXB2 were negatively correlated (r2 = -0.42, P = 0.01). After the treatment period significant decreases from baseline values were noted for PAI (P = 0.01), ET-1 (P = 0.006), TXB2 (P = 0.02), F2-isoprostanes (P = 0.01) and albuminuria (P = 0.01) in aPL participants but not in controls. These pilot data support oxidative sensitive mechanisms and a potential role for antioxidant treatment in the pathogenesis of aPL induced vasculopathy.
Ames
P R
PR
Coagulation Unit, Cardarelli Hospital, Naples, Italy. pames@rayne.umds.ac.uk
Tommasino
C
C
Alves
J
J
Morrow
J D
JD
Iannaccone
L
L
Fossati
G
G
Caruso
S
S
Caccavo
F
F
Brancaccio
V
V
D000328:Adult; D000419:Albuminuria; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000925:Anticoagulants / Q000494:pharmacology; D000975:Antioxidants / Q000627:therapeutic use*; D016736:Antiphospholipid Syndrome / Q000188:drug therapy* / Q000378:metabolism; D001095:Arachidonic Acids / Q000652:urine; D003404:Creatinine / Q000378:metabolism; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000652:urine; D010865:Pilot Projects; D011341:Probucol / Q000627:therapeutic use*; D011516:Prothrombin / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism; D013929:Thromboxane B2 / Q000652:urine; D014859:Warfarin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000032:analysis
D017152:Antibodies, Antiphospholipid; D000924:Anticholesteremic Agents; D000925:Anticoagulants; D000975:Antioxidants; D001095:Arachidonic Acids; D019332:Endothelin-1; D008055:Lipids; D014841:von Willebrand Factor; D009569:Nitric Oxide; D013929:Thromboxane B2; D014859:Warfarin; D011516:Prothrombin; D003404:Creatinine; D011341:Probucol