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Cyclic-AMP agonists inhibit antiphospholipid/beta2-glycoprotein I induced synthesis of human platelet thromboxane A2 in vitro

Opara, R.; Robbins, D.L.; Ziboh, V.A.

Journal of Rheumatology 30(1): 55-59

2003

ISSN/ISBN: 0315-162X
PMID: 12508390
Document Number: 565800
Objective: To investigate mechanisms responsible for increased thrombotic activity in systemic lupus erythematosus (SLE) associated with the antiphospholipid syndrome (APS). We had reported that anticardiolipin/beta2-glycoprotein I (aCL/beta2-GPI) complexes induce platelet overactivity resulting in excessive production of thromboxane A2 (TXA2). Presumably this occurs by decreased platelet cyclic AMP (cAMP) activity and results in increased platelet aggregation. Methods: We stimulated platelet intracellular cAMP generation with known cAMP agonists (dibutyryl cAMP, theophylline, and prostaglandin E1) and measured aCL/beta2-GPI induced platelet TXB2 production in vitro. Isolated human platelets were prelabeled with 14C-arachidonic acid and then challenged with aCL/beta2-GPI in the presence or absence of cAMP-activating substances. The resulting 14C labeled TXB2 was quantified by thin layer chromatography and radioactive scanning. Results: We found a marked decrease in aCL/beta2-GPI induced platelet TXB2 production by the cAMP agonists in a dose dependent manner. Conclusion: Our findings suggest the usefulness of cAMP agonists in the control of thrombosis in some patients with SLE and APS.

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