Tissue factor gene expression in the adipose tissues of obese mice
Tissue factor gene expression in the adipose tissues of obese mice
复制标题
DOI：
10.1073/pnas.95.13.7591
复制
发表时间：
1998-06-23
影响因子：
11.1
通讯作者：
Loskutoff, DJ
中科院分区：
文献类型：
--
作者：
Samad, F;Pandey, M;Loskutoff, DJ
肥胖患者纤溶和凝血级联反应的蛋白质表达改变可能导致与这种疾病相关的心血管风险。我们以前报道，纤溶酶原激活物抑制剂1（派-1）是显着上调的遗传性肥胖小鼠的血浆和脂肪组织。这种变化可能会扰乱正常的止血平衡，并造成严重的低纤溶状态。在这里，我们表明，组织因子（TF）基因的表达也显着升高，在附睾和皮下脂肪垫从ob/ob小鼠相比，他们的瘦同行，其在肥胖小鼠的表达水平随着年龄的增长和肥胖的程度。脂肪组织的细胞分离和原位杂交分析表明，TF mRNA在脂肪细胞和未鉴定的基质血管细胞中增加。已知转化生长因子β（TGF-β）在肥胖小鼠的脂肪组织中升高，并且施用TGF-β增加体内和体外脂肪细胞中TF mRNA的表达。这些观察结果提高了TF和TGF-β可能导致伴随肥胖和相关非胰岛素依赖型糖尿病的心血管疾病增加的可能性，并且脂肪细胞在此过程中起关键作用。最近证明TF也影响血管生成、细胞粘附和信号传导，表明其在脂肪组织生理学/病理学中的确切作用可能是复杂的。
Altered expression of proteins of the fibrinolytic and coagulation cascades in obesity may contribute to the cardiovascular risk associated with this condition. We previously reported that plasminogen activator inhibitor 1 (PAI-1) is dramatically up-regulated in the plasma and adipose tissues of genetically obese mice. This change may disturb normal hemostatic balance and create a severe hypofibrinolytic state. Here we show that tissue factor (TF) gene expression also is significantly elevated in the epididymal and subcutaneous fat pads from ob/ob mice compared with their lean counterparts, and that its level of expression in obese mice increases with age and the degree of obesity. Cell fractionation and in situ hybridization analysis of adipose tissues indicate that TF mRNA is increased in adipocytes and in unidentified stromal vascular cells. Transforming growth factor beta (TGF-beta) is known to be elevated in the adipose tissue of obese mice, and administration of TGF-beta increased TF mRNA expression in adipocytes in vivo and in vitro. These observations raise the possibility that TF and TGF-beta may contribute to the increased cardiovascular disease that accompanies obesity and related non insulin-dependent diabetes mellitus, and that the adipocyte plays a key role in this process. The recent demonstration that TF also influences angiogenesis, cell adhesion, and signaling suggests that its exact role in adipose tissue physiology/pathology, may be complex.