ABSTRACT
Cross talk between endothelial cells and adipocytes is vital to adipocyte functions, but little is known about the mechanisms or factors controlling the process. Angiogenesis is a critical component linking the endothelium to healthy adipogenesis, yet it is not known if or how it is involved in adipocyte physiology. Therefore, the purpose of this study was to determine the effect of angiopoietin-1 (Ang-1) and -2 (Ang-2) as well as their receptor, Tie-2, on adipocyte physiology. 3T3-L1 pre- and mature adipocytes were found to express Ang-1, Ang-2, and Tie-2, which decrease upon polyunsaturated fatty acid treatment. Furthermore, 3T3-L1 cells treated with recombinant Ang-1 or Ang-2 increased expression of the antiapoptotic gene Bcl-x and decreased expression of the proapoptotic gene Casp-8. Next, preadipocytes were treated with saturated fatty acids (SFAs) to induce cell stress. SFA-mediated splicing of X-box-binding protein-1 was reduced by co-treatment with Ang-1, and cell viability was improved in the presence of SFAsâ¯+â¯Ang-1. Taken together, these results indicate that Ang-1 may protect preadipocytes from SFA-induced apoptosis and endoplasmic reticulum stress.
Subject(s)
Adipocytes/drug effects , Adipogenesis , Adipose Tissue/cytology , Angiopoietin-1/pharmacology , Dietary Fats/pharmacology , Fatty Acids/pharmacology , Neovascularization, Physiologic , 3T3-L1 Cells , Adipocytes/metabolism , Adipocytes/physiology , Adipose Tissue/blood supply , Adipose Tissue/physiology , Angiopoietin-1/metabolism , Angiopoietin-2/metabolism , Angiopoietin-2/pharmacology , Animals , Apoptosis , Caspase 8/metabolism , Cell Survival , Endoplasmic Reticulum Stress , Endothelial Cells , Fatty Acids, Unsaturated/pharmacology , Humans , Macrophages , Mice , Mice, Inbred C57BL , Receptor, TIE-2/metabolism , Receptor, TIE-2/pharmacology , X-Box Binding Protein 1/metabolism , bcl-X Protein/metabolismABSTRACT
Angiogenesis is considered to be one of the most common mechanisms leading to ultrafiltration failure (UFF) in long-term peritoneal dialysis (PD) patients. The angiopoietin (Ang)/Tie system was found to play a role in the initiation of pathological neoangiogenesis and is also involved in peritoneal angiogenesis caused by peritoneal fluid. This aim of this study was to investigate the effects of the soluble Tie2 fusion protein (sTie2/Fc) on peritoneal angiogenesis in PD-treated uremic rats. The rats were divided into 6 groups: normal, sham surgery, uremic rats without PD, uremic PD-treated rats, uremic rats treated with PD and sTie2/Fc (0.25 µg/100 g) and uremic rats treated with PD and sTie2/Fc (0.5 µg/100 g). PD rats were treated once a day for 28 days prior to testing. Real-time polymerase chain reaction (RT-PCR) or tissue immunohistochemical staining was used to detect Ang-2 mRNA or protein expression in the peritoneal tissues of each group. The microvessel density (MVD) of the peritoneum was detected and quantified by immunohistochemical staining using the anti-CD34 antibody. Compared with the control group, Ang-2 mRNA and protein expression was significantly upregulated in the uremic and PD groups (P<0.05). MVD in the experimental group increased compared with the control group. sTie2/Fc treatment decreased the levels of Ang-2 mRNA and protein expression (P<0.05) in a dose-dependent manner and decreased PD-induced MVD in the peritoneum. In conclusion, angiogenesis of the peritoneum induced by PD was inhibited using sTie2/Fc in a uremic rat model.
