Increased tissue factor activity in monocytes from obese young adults

• Published in: Clinical and experimental pharmacology & physiology 2010-11, Vol.37 (11), p.1049-1054
• Main Authors: Ayer, Julian G, Song, Changjie, Steinbeck, Katherine, Celermajer, David S, Freedman, S Ben
• Format: Article
• Language: English
• Subjects: Adult; Case-Control Studies; Cell Culture Techniques; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Humans; inflammation; leptin; Leptin - pharmacology; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lipopolysaccharides - pharmacology; Male; obesity; Obesity - blood; Obesity - complications; Obesity - immunology; Obesity - metabolism; resistin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; serum amyloid A protein; Serum Amyloid A Protein - analysis; Serum Amyloid A Protein - immunology; thromboplastin; Thromboplastin - biosynthesis; Thromboplastin - immunology; Thrombosis - blood; Thrombosis - etiology; Thrombosis - immunology; Thrombosis - metabolism
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/j.1440-1681.2010.05430.x

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.