Bastelica Delphine, Mavri Alenka, Verdierl Monique, Berthet Bruno, Juhan-Vague Irène, Alessi Marie-Christine
Thromb Haemost. 2002 Sep;88(3):481-7.
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.
纤溶酶原激活物抑制剂1（PAI-1）是动脉粥样硬化的一个风险标志物，在肥胖受试者的脂肪组织中高表达。PAI-1也被视为一种急性期蛋白。最近，脂肪组织被描述为炎症细胞因子的一个来源。因此，我们的目的是研究肥胖（n = 60）和瘦（n = 28）受试者血浆和脂肪组织中PAI-1与白细胞介素-6（IL-6）、肿瘤坏死因子（TNF）、肿瘤坏死因子受体（TNFRSF1s）和转化生长因子β1（TGFβ1）之间的关系。研究已扩展至纤溶酶原激活物（组织型纤溶酶原激活物（t-PA）和尿激酶型纤溶酶原激活物（u-PA））。与瘦受试者相比，肥胖受试者所有研究参数的血浆水平均较高（TGFβ1除外），而在脂肪组织中，只有PAI-1、t-PA和TGFβ抗原水平存在差异。在肥胖人群中，血浆PAI-1水平与循环TNF弱相关，调整血浆t-PA后这种关系消失。脂肪组织PAI-1水平与TNFRSF1s和TGFβ呈正相关，与TNFRSF1A的关系最为显著，TNFRSF1A解释了PAI-1变异性的82%。TNF和IL-6分别是血浆和脂肪组织中t-PA变异性的主要影响因素。我们的结果表明TNFRSF1s在脂肪组织对PAI-1表达的调节中具有重要意义。主要由内皮细胞产生的t-PA与IL-6或TNF之间的关联表明炎症可能参与了脂肪组织中的血管生成。
