Increased tissue factor activity in monocytes from obese young adults.
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.
Ayer
Julian G
JG
Department Of Cardiology, Royal Prince Alfred Hospital, Australia.
Song
Changjie
C
Steinbeck
Katherine
K
Celermajer
David S
DS
Ben Freedman
S
S
D000328:Adult; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020738:Leptin / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000032:analysis / Q000276:immunology; D013925:Thromboplastin / Q000096:biosynthesis* / Q000276:immunology; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000378:metabolism
D020738:Leptin; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D013925:Thromboplastin