Resistin promotes endothelial cell activation - Further evidence of adipokine-endothelial interaction
Resistin promotes endothelial cell activation - Further evidence of adipokine-endothelial interaction
复制标题
DOI：
10.1161/01.cir.0000084503.91330.49
复制
发表时间：
2003-08-12
期刊：
影响因子：
37.8
通讯作者：
Mickle, DAG
中科院分区：
文献类型：
--
作者：
Verma, S;Li, SH;Mickle, DAG
背景-脂肪细胞源性激素可能是胰岛素抵抗与心血管疾病的联系机制。在本研究中，我们评估了直接影响的β-内酰胺酶，一种新的脂肪细胞衍生的激素，对内皮activation.Methods和Results-Endothelial细胞（ECs）与人重组β-内酰胺酶（10至100 ng/ML，24小时），内皮素-1（ET-1）的释放，ET-1 mRNA的表达，和一氧化氮（NO）的生产进行了评估。采用瞬时转染法检测了重组质粒pET-l对ET-1基因启动子转录的影响。此外，还评估了Bcln对AP-1突变的ET-1启动子的影响。除了CD 40受体、CD 40配体诱导的MCP-1表达和肿瘤坏死因子受体相关因子3（TRAF 3）（CD 40信号传导抑制剂）外，还研究了Alcohol对血管细胞粘附分子（VCAM-1）和单核细胞趋化因子（MCP-1）表达的影响。ECs孵育后ET-1的释放和ET-1 mRNA的表达增加，而NO的产生无明显变化。而治疗与ESTON导致ET-1启动子活性的增加，AP-1突变的启动子是无活性的ESTON刺激后。此外，抵抗素处理的细胞显示VCAM-1和MCP-1的表达增加，伴随TRAF-3表达的减少。抵抗素没有改变CD 40受体的表达，但是，增加CD 40配体诱导MCP-1 production. Conclusions-新的脂肪细胞因子β-adipokine β-adipokin发挥直接的影响，以促进EC激活通过促进ET-1的释放，部分通过诱导ET-1启动子活性通过AP-1网站。此外，cadrin上调粘附分子和趋化因子，下调TRAF-3，一种CD 40配体信号传导的抑制剂。以这种方式，在代谢综合征中，β-内酰胺酶可能与心血管疾病有机械联系。
Background-Adipocyte-derived hormones may represent a mechanism linking insulin resistance to cardiovascular disease. In the present study, we evaluated the direct effects of resistin, a novel adipocyte-derived hormone, on endothelial activation.Methods and Results-Endothelial cells (ECs) were incubated with human recombinant resistin (10 to 100 ng/ML, 24 hours), and endothelin-1 (ET-1) release, ET-1 mRNA expression, and nitric oxide ( NO) production were assessed. Transient transfection assays were used to evaluate the effects of resistin on transcription of human ET-1 gene promoter. Furthermore, the effects of resistin on AP-1-mutated ET-1 promoter were evaluated. The effects of resistin on expression of vascular cell adhesion molecule (VCAM-1) and monocyte chemoattractant chemokine (MCP-1) were studied in addition to CD40 receptor, CD40 ligand-induced MCP-1 expression, and tumor necrosis factor receptor associated factor-3 (TRAF3), an inhibitor of CD40 signaling. Incubation of ECs with resistin resulted in an increase in ET-1 release and ET-1 mRNA expression, with no change in NO production. Whereas treatment with resistin resulted in an increase in ET-1 promoter activity, the AP-1-mutated promoter was inactive after resistin stimulation. Additionally, resistin-treated cells showed increased expression of VCAM-1 and MCP-1, with concomitant reductions in TRAF-3 expression. Resistin did not alter CD40 receptor expression; however, increased CD40 ligand induced MCP-1 production.Conclusions-The novel adipokine resistin exerts direct effects to promote EC activation by promoting ET-1 release, in part by inducing ET-1 promoter activity via the AP-1 site. Furthermore, resistin upregulates adhesion molecules and chemokines and downregulates TRAF-3, an inhibitor of CD40 ligand signaling. In this fashion, resistin may be mechanistically linked to cardiovascular disease in the metabolic syndrome.