Antioxidant susceptibility of pathogenic pathways in subjects with antiphospholipid antibodies: a pilot study

Abstract

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-l (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 NO_x (r² ‘ÿ0.6, P ‘ 0.005) whereas urinary NO^x and TXB² were negatively correlated (r² ‘ÿ0.42, 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.

Keywords

antiphospholipid antibodies oxidation atherosclerosis microalbuminuria

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