title: Lack of evidence for secretion of plasminogen activator inhibitor-1 by human subcutaneous adipose tissue in vivo.
abstract: Circulating plasminogen activator inhibitor-1 (PAI-1) levels are elevated in patients with coronary heart disease and may play an important role in atherothrombosis. Levels are also raised in obese, hypertriglyceridaemic, or insulin-resistant subjects, which predispose people to coronary heart disease. It is unclear, though, which organ is responsible for PAI-1 secretion, either in health or disease. We measured arteriovenous differences across a subcutaneous adipose tissue bed in 25 subjects without coronary heart disease, which, combined with measures of adipose tissue blood flow, provides synthetic rates. There was no net increase in levels of PAI-1 activity (median change 0.23, interquartile range -0.59, 1.21 IU x L(-1), p=0.30) or of PAI-1 antigen (mean change -0.01, SD+/-2.93 ng x mL(-1), p=0.98) in these subjects. Assuming homogeneous production of PAI-1 by all adipose tissue beds, the contribution of adipose tissue to PAI-1 activity is 3.1% (interquartile range, -11.7, +7.0%) and to PAI-1 antigen 1.6% (interquartile range -14.5, +7.3%). Arteriovenous difference of PAI-1 activity and antigen did not relate to measures of obesity, triglyceride, insulin, fatty acids, or circulating concentrations or adipose tissue production of tumour necrosis factor-alpha or interleukin-6. We conclude that, at least in healthy subjects, subcutaneous adipose tissue does not contribute significantly to circulating levels of PAI-1.
authors.affiliation: Centre for Diabetes and Cardiovascular Risk, Department of Medicine, University College London Medical School, Whittington, Hospital, United Kingdom. j.yudkin@ucl.ac.uk
authors.forename: J S
authors.initials: JS
authors.lastname: Yudkin
authors.forename: S W
authors.initials: SW
authors.lastname: Coppack
authors.forename: K
authors.initials: K
authors.lastname: Bulmer
authors.forename: A
authors.initials: A
authors.lastname: Rawesh
authors.forename: V
authors.initials: V
authors.lastname: Mohamed-Ali
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply / Q000378:metabolism*; D000328:Adult; D000941:Antigens / Q000097:blood; D001158:Arteries; D001769:Blood / Q000378:metabolism; D015992:Body Mass Index; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D014680:Veins
chemical_list: D000941:Antigens; D017395:Plasminogen Activator Inhibitor 1