Upregulation of Monocyte Tissue Factor Activity Is Significantly Associated With Low-Grade Chronic Inflammation and Insulin Resistance in Patients With Metabolic Syndrome

Background: The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors closely linked to inflammation and insulin resistance (IR). Tissue factor (TF) is an initiator of the extrinsic coagulation cascade and is expressed on peripheral blood monocytes and macrophages in atherosclerotic plaques. Monocytes are the principle cells capable of TF synthesis. Therefore, TF plays an important role in both thrombosis and atherosclerosis. Elevated levels of lipopolysaccharide (LPS), a strong stimulator of TF, have been observed in patients with MetS. No study has investigated the relationship between monocyte TF activity and inflammation, and IR in MetS. Methods and Results: Peripheral blood mononuclear cells (PBMCs) were collected from 40 normal subjects and 77 patients with MetS. Mononuclear cell TF procoagulant activity (MPCA) was measured with and without 100 pg/ml LPS stimulation using a 1-stage clotting assay and expressed as the mean ± SD (mU TF/106 PBMCs). MPCA in MetS was significantly greater than in normal subjects (without LPS: 88.0±74.8 vs 52.6±9.8 mU TF/106 PBMCs, P<0.001; with LPS: 269.6±165.6 vs 158.6±42.8 mU TF/106 PBMCs, P<0.001). The LPS-stimulated log MPCA in MetS patients was significantly associated with homeostasis model assessment of IR (r=0.256, P=0.024) and log high-sensitivity C-reactive protein (r=0.332, P=0.003). Conclusions: Upregulation of monocyte TF is significantly associated with low-grade inflammation and IR in MetS. (Circ J 2010; 74: 572 - 577)