Cardiology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
Thromb Haemost. 2012 Sep;108(3):485-92. doi: 10.1160/TH11-11-0822. Epub 2012 Jun 28.
Plasminogen activator inhibitor type-1 (PAI-1) is one of the most important inhibitors of endogenous fibrinolysis. Adipose tissue is a suggested source of the elevated plasma levels of PAI-1 in obesity. The relation between PAI-1 and inflammation is of particular interest, but current knowledge regarding regulation of PAI-1 in adipose tissue is mainly based on animal studies or ex vivo experiments on human cultured adipocytes. So far, no study has described stimulated gene expression and protein synthesis of PAI-1 in vivo in human adipose tissue. We used open heart surgery as a model of acute systemic inflammation. Twenty-two male patients underwent blood sampling and omental and subcutaneous adipose tissue biopsies for gene expression studies before and after surgery. Expression and localisation of PAI-1 antigen was evaluated by immunohistochemistry. After surgery gene expression of PAI-1 increased 27-fold in omental adipose tissue and three-fold in subcutaneous adipose tissue, but no differences were found in tissue-type plasminogen activator (t-PA) mRNA. PAI-1 antigen was localised within endothelial cells and in the adipose tissue interstitium close to vessels. The upregulated gene expression and protein synthesis in adipose tissue was followed by increased concentrations of PAI-1 antigen in plasma. In conclusion, we present for the first time that an acute systemic inflammation in humans increased gene expression and protein synthesis of PAI-1 in adipose tissue and that this increase was most prominent in omental adipose tissue. PAI-1 synthesis in adipose tissue due to acute systemic inflammation may be a link between inflammation and impaired endogenous fibrinolysis.
纤溶酶原激活物抑制剂-1（PAI-1）是内源性纤维蛋白溶解最重要的抑制剂之一。脂肪组织被认为是肥胖患者血浆 PAI-1 水平升高的来源。PAI-1 与炎症的关系特别引人关注，但目前关于脂肪组织中 PAI-1 调节的知识主要基于动物研究或人类培养脂肪细胞的离体实验。到目前为止，还没有研究描述过 PAI-1 在人类脂肪组织中的基因表达和蛋白质合成的刺激。我们使用心脏直视手术作为急性全身炎症的模型。22 名男性患者在手术前后进行了血液取样和网膜和皮下脂肪组织活检，用于基因表达研究。免疫组织化学评估了 PAI-1 抗原的表达和定位。手术后，网膜脂肪组织中 PAI-1 的基因表达增加了 27 倍，皮下脂肪组织增加了 3 倍，但组织型纤溶酶原激活物（t-PA）mRNA 没有差异。PAI-1 抗原定位于内皮细胞和靠近血管的脂肪组织间质中。脂肪组织中上调的基因表达和蛋白质合成伴随着血浆中 PAI-1 抗原浓度的增加。总之，我们首次提出，人类急性全身炎症增加了脂肪组织中 PAI-1 的基因表达和蛋白质合成，并且这种增加在网膜脂肪组织中最为明显。急性全身炎症导致的脂肪组织 PAI-1 合成可能是炎症和内源性纤维蛋白溶解受损之间的联系。
