Acetylsalicylic acid inhibits anticardiolipin antibody-induced platelet-activating factor (PAF) synthesis.
Enhanced endothelial cell PAF synthesis has been identified as a consequence of anticardiolipin antibody (ACA)-positive serum exposure. We proposed this observation as a contributing factor to thrombogenesis in women with the antiphospholipid syndrome. Since acetylsalicylic acid (ASA) is an accepted therapeutic alternative in these patients, we sought to determine if ASA would attenuate endothelial cell PAF production resulting from ACA exposure. Using primary, confluent monolayers of umbilical vein endothelial cells, experiments were performed to evaluate PAF synthesis after incubation with antibody-positive serum and ASA. Total PAF and its radyl-derivatives (1-alkyl- and 1-acyl-PAF) were quantified by tritiated acetate incorporation, phospholipid extraction, thin-layer chromatography and scintillation spectroscopy. ASA consistently decreased ACA-induced PAF synthesis (No ASA, 9573 +/- 443 vs 1mmol/L ASA, 4829 +/- 838 dpm/ml; p = 0.016) and the observed reduction was dose-dependent over a range of ASA concentrations (0.1, 1, 10 and 100 mmol/L; ANOVA, p = .00015). Reduced PAF synthesis was also observed in cultures exposed to ASA and incubated with antibody-negative serum. These observations suggest that in ACA-positive women, the antithrombotic effects of ASA may relate in part, to reduced endothelial cell PAF synthesis.
Silver
R K
RK
Division of Maternal-Fetal Medicine, Northwestern University Medical School, Evanston Hospital, Illinois 60201.
O'Connell
P D
PD
Caplan
M S
MS
D017153:Antibodies, Anticardiolipin / Q000502:physiology*; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000276:immunology; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*
D017153:Antibodies, Anticardiolipin; D010972:Platelet Activating Factor; D011464:Epoprostenol; D001241:Aspirin