Abstract 474: Metabolic Syndrome contributes to Aspirin-Resistant Thromboxane Biosynthesis via Inducing Platelets COX-2 Expression in Patients with Stable Angina
Background A large number of patients still experience a vascular event despite aspirin treatment. Cyclooxygenase-1 (COX-1), but not COX-2, is expressed in human platelets, and thromboxane A2 (TXA2) produced via COX-1 induces platelet aggregation and development of atherosclerosis. Cyclooxygenase-2 (COX-2)-mediated prostaglandin production is also associated with inflammation and atherosclerosis. The aim of this study is to clarify the relationship between aspirin resistant thromboxane synthesis and platelet COX-2 in metabolic syndrome.
Methods and Results 40 consecutive patients with stable coronary artery disease who had taken 100mg of aspirin for previous seven days were enrolled into this study (mean age64±7.5 years). Urinary 11-dehydro-thromboxane B2 (11-d-TXB2), a stable metabolite of thromboxane A 2 was measured. Patients with metabolic syndrome (group M) show higher 11-d- TXB2 levels compared with patients without metabolic syndrome (group Non-M, group M vs. group non-M 47.2±15.2 vs. 26.5±18.4 P<0.01). We also evaluated inducible isoform of cyclooxygenase in platelets, COX-2 expression to confer aspirin resistance. Possible contamination with extraplatelet sources of COX-2, is an issue of concern in COX-2 analysis. We have therefore established a flow cytometric analysis using monoclonal antibody against a peptide from the COX-2 amino acid sequence which is not present in COX-1. In fact, immunoreactive intra-platelet COX-2 was significantly increased in group M.
Conclusions In aspirin treated patients with stable angina, metabolic syndrome contributs to aspirin-resistant thromboxane biosynthesis via inducing platelets COX-2 expression.