title: Relationships between fibrinolytic and inflammatory parameters in human adipose tissue: strong contribution of TNFalpha receptors to PAI-1 levels.
abstract: Plasminogen activator inhibitor type 1 (PAI-1), a risk marker of atherosclerosis, is highly expressed in adipose tissue from obese subjects. PAI-1 is also considered as an acute phase protein. Recently, adipose tissue has been described as a source of inflammatory cytokines. Therefore, our aim was to study the relationships between PAI-1, and IL-6, TNF, TNF receptors (TNFRSF1s) and TGFbeta1, in plasma and adipose tissue from obese (n = 60) and lean (n = 28) subjects. Study has been extended to plasminogen activators (t-PA and u-PA). Compared to lean subjects, obese subjects exhibited higher plasma levels of all the studied parameters (except for TGFbeta1) whereas in adipose tissue only PAI-1, t-PA and TGFbeta antigen levels differed. In the obese population, plasma PAI-1 levels were weakly associated with circulating TNF, and this relationship disappeared after adjustment for plasma t-PA. Adipose tissue PAI-1 levels were positively associated with TNFRSF1s and TGFbeta, the strongest relationship being observed with TNFRSF1A, which explained 82% of PAI-1 variability. TNF and IL-6 were the main contributors to t-PA variability in plasma and in adipose tissue, respectively. Our results argue on the relevance of TNFRSF1s in the regulation of PAI-1 expression by adipose tissue. Association between t-PA, which is mainly produced by endothelial cells, and IL-6 or TNF suggest that inflammation might be involved in angiogenesis in adipose tissue.
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry*; D000328:Adult; D015703:Antigens, CD / Q000032:analysis / Q000097:blood / Q000502:physiology*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000097:blood / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000097:blood
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D010959:Tissue Plasminogen Activator