Increased tissue factor activity in monocytes from obese young adults

Abstract

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±4years, body mass index 46.0±8.7kg/m(2) ) and 12 age- and sex-matched lean controls were cultured either unstimulated or stimulated by lipopolysaccharide (LPS; 10ρg/mL and 100ng/mL, for 4-16h) or SAA (1 ng/mL, 25ng/mL, 250ng/mL, for 4h). Separately, PBMC from lean subjects were cultured unstimulated with leptin (100ρg/mL, 1ng/mL, 10ng/mL, 100ng/mL, 1 μg/mL), resistin (0.1ng/mL, 1ng/mL, 10ng/mL, 100ng/mL) or leptin (100ng/mL) plus LPS (100ρg/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±4.7mu TF/10(6) PBMC, P=0.01). After 4h 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.