Increased tissue factor activity in monocytes from obese young adults

Summary 1. The relationship between inflammation, obesity-related proteins and tissue factor (TF), the major initiator of the extrinsic clotting cascade, is not well understood. We examined if basal and stimulated peripheral blood mononuclear cell (PBMC) TF-procoagulant activity (PCA) was higher in obese subjects and examined the effects of leptin, resistin and serum amyloid A (SAA). 2. PBMC from 12 obese (six male, aged 29 ± 4 years, body mass index 46.0 ± 8.7 kg/m2) and 12 age- and sex-matched lean controls were cultured either unstimulated or stimulated by lipopolysaccharide (LPS; 10 ρg/mL and 100 ng/mL, for 4–16 h) or SAA (1 ng/mL, 25 ng/mL, 250 ng/mL, for 4 h). Separately, PBMC from lean subjects were cultured unstimulated with leptin (100 ρg/mL, 1 ng/mL, 10 ng/mL, 100 ng/mL, 1 μg/mL), resistin (0.1 ng/mL, 1 ng/mL, 10 ng/mL, 100 ng/mL) or leptin (100 ng/mL) plus LPS (100 ρg/mL). TF-PCA was determined by a 1-stage plasma recalcification assay. 3. Four-hour unstimulated PBMC TF-PCA was greater in the obese (90.4 ± 16.5 vs 39.9 ± 4.7 mu TF/106 PBMC, P = 0.01). After 4 h stimulation with SAA or LPS the TF-PCA was similar. Unstimulated TF-PCA correlated with log serum high sensitivity C- reactive protein (hs-CRP) (r = 0.42, P = 0.04) and insulin (r = 0.44, P = 0.048), but not with log serum SAA (r = 0.192, P = 0.55). Physiological concentrations of leptin or resistin and leptin plus LPS did not increase TF-PCA in PBMC from lean subjects. 4. Basal PBMC TF-PCA is higher in the obese and is associated with serum hs-CRP. The obesity-related proteins SAA, leptin and resistin are unlikely to play a major role in increasing PBMC TF-PCA.