PPARα Activators Inhibit Tissue Factor Expression and Activity in Human Monocytes

摘要: Background—Tissue factor (TF), expressed on the surface of monocytes and macrophages in human atherosclerotic lesions, acts as major procoagulant initiating thrombus formation acute coronary syndromes. Peroxisome proliferator–activated receptor-α (PPARα), a nuclear receptor family member, regulates gene expression response to certain fatty acids fibric acid derivatives. Given that some these substances reduce TF activity patients, we tested whether PPARα activators limit responses monocytic cells. Methods Results—Pretreatment freshly isolated or monocyte-derived with WY14643 eicosatetraynoic (ETYA) led reduced lipopolysaccharide (LPS)-induced concentration-dependent manner (maximal reduction 43±8% 250 μmol/L [P 0.05, n=3]). Two different PPARγ (15-deoxy_Δ12,14-prostaglandin J2 BRL49653) lacked similar effects. WY1464...