Relationships between fibrinolytic and inflammatory parameters in human adipose tissue: strong contribution of TNFalpha receptors to PAI-1 levels

Thromb Haemost. 2002 Sep;88(3):481-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / chemistry*
  • Adult
  • Antigens, CD / analysis
  • Antigens, CD / blood
  • Antigens, CD / physiology*
  • Biomarkers / analysis
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Fibrinolysis
  • Humans
  • Inflammation
  • Interleukin-6 / analysis
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / metabolism
  • Obesity / pathology*
  • Plasminogen Activator Inhibitor 1 / analysis*
  • Plasminogen Activator Inhibitor 1 / blood
  • Receptors, Tumor Necrosis Factor / analysis
  • Receptors, Tumor Necrosis Factor / blood
  • Receptors, Tumor Necrosis Factor / physiology*
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tissue Plasminogen Activator / analysis
  • Tissue Plasminogen Activator / blood

Substances

  • Antigens, CD
  • Biomarkers
  • Interleukin-6
  • Plasminogen Activator Inhibitor 1
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • TNFRSF1B protein, human
  • Tissue Plasminogen Activator